IGF2BP2 Research Articles

IGFBP6 Modulates Proteostasis by Activating ATF4 Targets and Reducing ER Retrotranslocon Expression.

Reduced expression of the IGFBP6 protein leads to an increase in the metastatic potential of breast cancer (BC) cells. The level of protein synthesis in tumor cells is increased, leading to a compensatory adjustment of proteostasis. One of the tools used to study proteostasis is protein toxins of the RIP-II family, which irreversibly inactivate ribosomes (particularly, viscumin). We investigated the effect of IGFBP6 gene knockdown on the proteostasis in the BC cell line MDA-MB-231. Ribosomes from MDA-MB-231IGFBP6 cells, knockdown for the IGFBP6 gene, are less efficiently modified by the toxin. This is probably due to the reduced transport of the viscumin catalytic subunit from the ER to the cytoplasm. MDA-MB-231IGFBP6 cells showed reduced expression of the retrotranslocon HRD1/Derlin subunit, which is a component of the ER-associated protein degradation system (ERAD). For ATF4 transcription factor, which is a part of the ER unfolded protein response (UPR) pathway, an increased expression of its targets was found.

The utility of Insulin Like Growth Factor Binding Proteins (IGFBPs-1, 2, 3) with genes expression in resistance to Imatinib and Nilotinib in chronic myeloid leukemia: a pilot study from Delta Egypt

Introduction: Resistance to tyrosine kinase inhibitors (TKIs) is an obstacle facing CML patients in spite of the high cure rate. In this context, a study association between IGFBP (1, 2, 3) genes expression and their proteins in CML with the response to TKI has been implicated. Patients and methods: 115 newly diagnosed CML in chronic phase (CP) followed up over 12 months under TKI. 116 apparently healthy individuals were used as a control. RT-qPCR amplification was used for detecting IGFBPs genes expression, and ELISA technique was used for measuring serum IGFBPs. Results: IGFBP-1 and IGFBP-3 genes expression, as well as their serum levels, were significantly higher in CML patients, whereas IGFBP-2 gene expression was not. Interestingly, IGFBP-1 gene expression and IGFBP-1 serum levels were significantly higher in resistant patients compared to responder patients. However, the expression of IGFBP-2, 3 genes and their serum were insignificant. Conclusion: IGFBP-1 gene expression and its serum were significantly correlated with resistance. It is currently recommended that IGF-receptor inhibitors be developed and utilized. We are hoping to optimize the cure rate for CML treated with TKIs. Keywords: IGFBP-1-3; Gene expression; CML; Imatinib; Nilotinib.

Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression

There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.

IGFBP5 in osteosarcoma tumorigenesis: Gene expression profile among metastatic and non-metastatic patients

Osteosarcoma (OS) is the most frequent primary malignant bone tumor among children and adolescents, with a peak of incidence in the second decade of life. The presence of metastasis at diagnosis in OS patients significantly decreases the chances of survival and new therapy approaches are needed. The IGFBP5 gene is related to osteoblasts metabolism and some studies have pointed out a role of its low expressions in OS development and metastasis. In this study, we aimed to establish an IGFBP5 gene expression profile among metastatic and non-metastatic OS patients throughout the treatment and development of the disease. Fresh-frozen tumor samples were obtained from 40 patients admitted to treatment at the Pediatric Oncology Institute (IOP/GRAACC/UNIFESP) and divided by clinical status: metastatic or non-metastatic disease. For each patient, samples before and after chemotherapy treatment were obtained, as well as metastasis and lung tissue surrounding metastasis samples from the metastatic patients. A quantitative real-time PCR was used to investigate IGFBP5 expression. Our analyses demonstrate that non-metastatic patients presented lower IGFBP5 expression in their pre-chemotherapy samples compared with metastatic patients, suggesting that low expressions of this gene could help triggering the OS tumorigenesis but that its action alone is not sufficient to activate the metastatic process. Heterogeneity in IGFBP5 expressions within groups was also seen. We observed that IGFBP5 and two MAPK genes, a downstream pathway in the IGFBP5 axis, are differentially expressed in OS samples of non-metastatic patients. Further investigation about these genes’ modulations might lead to a better understanding of metastasis development in OS.

Investigating the Impact of Fasting and Refeeding on Blood Biochemical Indicators and Transcriptional Profiles in the Hypothalamus and Subcutaneous Adipose Tissue in Geese.

Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fasting and refeeding on blood biochemical indicators and transcriptional profiles in the hypothalamus and subcutaneous adipose tissue of geese. Biochemical assays reveal that fasting significantly increases levels of free fatty acids and glucagon, while reducing concentrations of triglycerides, leptin, and insulin. Transcriptomic analyses identify a complex transcriptional response in both the hypothalamus and subcutaneous adipose tissue, affecting several metabolic pathways and key genes associated with feed intake and energy metabolism. In subcutaneous adipose tissue, fasting downregulates genes involved in fatty acid synthesis (LPL, SCD, and ACSL1) and upregulates PLIN2, a gene promoting lipid droplet degradation. Fasting affects a variety of metabolic pathways and critical genes in the hypothalamus, including Apelin, insulin, and mTOR signaling pathways. After fasting, the mRNA expression of NOG, GABRD, and IGFBP-1 genes in the hypothalamus are significantly upregulated, while proopiomelanocortin (POMC) gene expression is markedly downregulated. This study highlights the intricate biological responses to nutritional changes in geese, which adds to our understanding of energy balance and metabolic regulation in avian species.

The effects of the feeding duration of propylene glycol on major meat quality parameters and substantial proteins in the muscle of Akkaraman lambs

In this study, the effects of propylene glycol (PG) on meat quality and molecular pathways related to energy metabolism in longissimus lumborum muscle on lambs were evaluated. Seventy-two lambs were divided into three groups consisting of 60th, 90th, and 120th of slaughter days. The dosage of the PG and slaughter days were the variables used in the study. Eight animals were slaughtered from each group on each day. The meat quality parameters (e.g., pH, protein, fatty acid profile) and IGF-1, IGFBP4, and DGAT1 (i.e., mRNA and protein levels) were evaluated. The pH 45 min post-slaughter was higher in PG groups on 120th day. On the 4th day after slaughter, the b value was the lowest in the PG3, while 7th day after slaughter it was highest in Con and PG3 on 90th day. The total n3 and n6 were lowest and the NV was highest on 120th day. The IGFBP4 was upregulated in the PG groups on all of the slaughter days. The DGAT1 was upregulated in the PG3 on the 90th day. The IGF-1, DGAT1, IGFBP4 protein levels were found to have increased in the PG3 on 90th day. The IGFBP4 was found to have decreased in the PG3 on 120th day. According to the results of the study, the oral administration of the PG at the 3 mL/kg live weight0.75 for at least 120 days may have positive effects on meat quality in lambs through the IGF-1, DGAT1, and IGFBP4 genes and the proteins encoded by these genes.

IGFBP6 regulates extracellular vesicles formation via cholesterol abundance in MDA-MB-231 cells

Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6 expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential. In addition, the knockdown of IGFBP6 leads to impaired lipid metabolism. In this study, we demonstrated that the knockdown of the IGFBP6 gene, a highly selective inhibitor of IGF-II, led to a significant decline in the number of secreted extracellular vesicles (EVs) and altered cholesterol metabolism in MDA-MB-231 cells. Knockdown of IGFBP6 led to a decrease in the essential proteins responsible for the biogenesis of cholesterol LDLR and LSS, which reduced the amount by more than 13 times. In addition, the knockdown of IGFBP6 led to a possible change in the profile of adhesion molecules on the surface of EVs. The expression of L1CAM, IGSF3, EpCAM, CD24, and CD44 decreased, and the expression of EGFR increased. We can conclude that the negative prognostic value of low expression of this gene could be associated with increased activity of IGF2 in tumor-associated fibroblasts due to low secretion of IGFBP6 by tumor cells. In addition, changing the profile of adhesion molecules on the surface of tumor EVs may contribute to the more efficient formation of metastatic niches.

The effects of Panax ginseng on growth enhancement, innate immunity, and microbiome profiling in Penaeus vannamei

BackgroundIn aquaculture, feed additives are widely explored. Among them, Panax ginseng Meyer, a natural herbal remedy, has demonstrated its efficacy in many aquaculture species. However, research regarding Penaeus vannamei shrimp, one of the most significant species in aquaculture, remains limited. MethodsThis study investigates the benefits of P. ginseng for P. vannamei, specifically its effects on growth, innate immunity, and shrimp microbiome. Juvenile P. vannamei were fed commercial feed mixed with red ginseng extract at 5 concentrations (0.00 %, 0.05 %, 0.10 %, 0.50 %, and 1.00 %) for 6 weeks. Body weight was measured on days 21 and 42. On day 42, three shrimp per group were selected for further analysis. ResultsIn the growth study, Group 0.10 % displayed significantly improved FBW, WG, SGR, and FCR compared to those in Group 0.00 % on day 42. The qPCR assay showed significantly higher IGF-BP gene expression in Groups 0.05 %, 0.10 %, and 1.00 % compared to Group 0.00 %. In the innate immunity analysis, SOD activity was significantly higher in Groups 0.05 % and 0.50 % compared to that in Group 0.00 %. In the bacterial community analysis, Group 0.10 % exhibited higher Flavobacteriaceae and lower Vibrionaceae at the family level compared to Group 0.00 %. At the genus level, Group 0.10 % showed increased unspecified Flavobacteriaceae and decreased Vibrio compared to Group 0.00 %. ConclusionAdding P. ginseng to the feed enhanced growth, immune response, and microbiome composition in P. vannamei. Further research on refining dosage levels and utilizing red ginseng residues could boost commercial productivity and economic benefits in aquaculture practices.

Identification of disease-specific genes related to immune infiltration in nonalcoholic steatohepatitis using machine learning algorithms.

To identify disease signature genes associated with immune infiltration in nonalcoholic steatohepatitis (NASH), we downloaded 2 publicly available gene expression profiles, GSE164760 and GSE37031, from the gene expression omnibus database. These profiles represent human NASH and control samples and were used for differential genes (DEGs) expression screening. Two machine learning methods, the Least Absolute Shrinkage and Selection Operator regression model and Support Vector Machine Recursive Feature Elimination, were used to identify candidate disease signature genes. The CIBERSORT deconvolution algorithm was employed to analyze the infiltration of 22 immune cell types in NASH. Additionally, we constructed a NASH cell model using HepG2 cells treated with oleic acid and free fatty acids. The construction of the cell model was verified using oil red O staining, and Western blotting was used to detect the protein expression of the disease signature genes in both control and model groups. As a result, a total of 262 DEGs were identified. These DEGs were primarily associated with metal ion transmembrane transporter activity, sodium ion transmembrane transporter protein activity, calcium ion, and neuroactive ligand-receptor interactions. FOS, IGFBP2, dual-specificity phosphatase 1 (DUSP1), and IKZF3 were identified as disease signature genes of NASH by the least absolute shrinkage and selection operator and Support Vector Machine Recursive Feature Elimination algorithms for DEGs analysis. The receiver operating characteristic curves showed that FOS, IGFBP2, DUSP1, and IKZF3 had good diagnostic value (area under receiver operating characteristic curve > 0.8). These findings were validated in the GSE89632 dataset and through cellular assays. Immunocyte infiltration analysis revealed that NASH was associated with CD8 T cells, CD4 T cells, follicular helper T cells, resting NK cells, eosinophils, regulatory T cells, and γδ T cells. The FOS, IGFBP2, DUSP1, and IKZF3 genes were specifically associated with follicular helper T cells. Lipid droplet aggregation significantly increased in HepG2 cells treated with oleic acid and free fatty acids, indicating successful construction of the cell model. In this model, the expression of FOS, IGFBP2, and DUSP1 was significantly decreased, while that of IKZF3 was significantly elevated (P < .01, P < .001) compared with the control group. Therefore, FOS, IGFBP2, DUSP1, and IKZF3 can be considered as disease signature genes associated with immune infiltration in NASH.

The effect of IGFBP3 gene knockout by the CRISPR/Cas9 system on the IGF-1 pathway in murine cells

BackgroundThe IGF-1 signaling pathway has been deeply involved in the aging mechanism. The insulin-like growth factor binding protein 3 (IGFBP-3) is a protein that binds to IGF-1 that regulates growth, survival, and aging. ObjectiveThe purpose of this study was to investigate the impact of the IGFBP3 gene knockout (KO) on the expressions of aging-related proteins and genes using the CRISPR/Cas9 system. MethodsThe IGFBP3 gene knockout (KO) was performed by the CRISPR/Cas9 system. Sanger DNA sequencing and Indel analyses were used to verify the induction of mutation. ResultsFirst, Sanger DNA sequencing was used to analyze the IGFBP3 gene knockout in murine cells (B16F1). The isolation of three colonies with the mutated DNA sequences in the IGFBP3 gene was validated. In addition, the expression levels of the IGFBP3 gene and protein in the edited B16F1 cells were lower than in those of normal B16F1 cells in western blot analysis as well as RT-PCR and qPCR. Moreover, IGFBP3 gene KO cells enhanced the level of SA-ß-gal staining and short telomere length compared to normal B16F1 cells. In particular, it was found that the expression levels of senescence-related proteins such as PI3K, AKT1, PDK1, and p53 were higher in IGFBP3 gene KO cells than in normal cells in both the absence and presence of IGF-1. ConclusionsTherefore, the above findings could provide a clue that IGFBP3 could play a key role in the aging mechanism.

The associations of IGF2, IGF2R and IGF2BP2 gene polymorphisms with gestational diabetes mellitus: A case-control study.

To investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population. A total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24-28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk. There were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01). IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

Gene expression analyses of GH/IGF axis in triploid crucian carp with growth heterosis.

Hybridization and polyploid breeding are the main approaches used to obtain new aquaculture varieties. Allotriploid crucian carp (3n) with rapid growth performance was generated by mating red crucian carp (RCC) with allotetraploids (4n). Fish growth is controlled by the growth hormone (GH)/insulin-like growth factor (IGF) axis. In the present study, we examined the expression characteristics of GH/IGF axis genes in hybrids F1, 4n, 3n, RCC and common carp (CC). The results showed that GHRa, GHRb, IGF1, IGF2, and IGF-1Ra were highly expressed in 3n compared with RCC and CC, whereas IGF3 was undetectable in the liver in RCC, CC and 3n. GHRa and GHRb had low expression in the 4n group. In hybrid F1, GHRa expression was low, whereas GHRb was highly expressed compared to the levels in RCC and CC. Moreover, in hybrid F1, the expression of IGF3 was higher, and the expression of IGF1 and IGF2 was lower than that in the RCC and CC, whereas the expression of IGF-1Ra was similar to that in RCC and CC. For the IGFBP genes, IGFBP1 had higher expression in 3n compared than that in RCC and CC, while other IGFBP genes were not high expressed in 3n. Among the genes detected in this study, 11 genes were nonadditively expressed in 3n, with 5 genes in the transgressive upregulation model. We proposed that the 11 nonadditive expression of GH/IGF axis genes is related to growth heterosis in 3n. This evidence provides new insights into hybridization and polyploid breeding from the perspective of hormone regulation.

Abstract 1645: Telomere-related genes associated with clinical-pathological in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) stands as one of the leading causes of cancer deaths worldwide. Studies have suggested that telomeres shortening is linked to genetic instability, higher risk of developing pancreatic cancer and pancreatic tumorigenesis. However, previous research has predominantly focused on either telomere length or specific telomere-related genes in pancreatic cancer. Therefore, it is essential to elucidate the association between telomere-related genes and pancreatic cancer to identify novel therapeutic strategies and establish prognostic biomarkers. Telomere-relevant genes were downloaded from the TelNet database. Expression data from primary tumour of The Cancer Genome Atlas-PAAD (TCGA-PAAD) cohort, the Genome Sequence Archive CRA001160 dataset and the GTEx database were obtained for screen for differentially expressed genes (DEGs). Gene set enrichment analisis was performed using the Enrichr software. The gene essentiality queried from the gene dependency database of the Achilles-DepMap project was also assessed. Finally, data of The Cancer Genome Atlas-PanCancer CaPa cohort and healthy pancreas from the GTEx database, obtained from the UCSC Xena project, were used to correlate gene expression with stemness signatures and clinical-pathological variables. We identified 300 telomere-associated DEGs, Of these, 73 genes were common to studies and they were to be enriched in biological processes related to the cell cycle and telomere homeostasis. The differentially expresed of ASS1, S100P, IGF2BP2, MET, ABCC3 and RAC1 genes were significantly associated with overall survival and recurrence-free survival, conferring them prognostic value. Furthermore, the expression profiles of these genes are significantly associated with the histological grade of the disease, as well as with tumour T-N classification, the presence of residual tumour, the degree of response to treatment and stemness signatures. Among these, three genes of particular interest (KLF3, RAC1 and ABI1) were identified and shown to be highly essential in pancreatic cancer cell lines. In summary, we have identified a telomere gene-related signature for pancreatic cancer, highlighting the prognostic value of KLF3, RAC1, and ABI1 genes. This signature is significantly associated with clinical-pathological variables of the disease, potentially offering new insights for individualized therapy. Citation Format: Erika Curiel Gómez, Vilma Maldonado Lagunas, Jorge Meléndez Zajgla. Telomere-related genes associated with clinical-pathological in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1645.

Abstract 1024: Differential gene expression of colorectal cancer biomarkers in Hispanic individuals

Abstract Colorectal cancer (CRC) is a leading cause of cancer death among men and women in Puerto Rico and the United States. About 60-70% of CRC cases are found at advanced stages (III/IV), suggesting limited adherence to available screening methods. Several molecular biomarkers have been identified as discriminatory for CRC (e.g., KRAS, NRAS, MSI), improving CRC management and patient outcomes. This study evaluates the differential expression patterns of DKK3, PKM2, IGFBP2, and SEPT9 genes between matched CRC tumors and adjacent mucosa samples. The secondary outcome was to examine the association between the presence of the selected biomarkers in tissue compared to blood samples. Using a retrospective study design, we examined 112 tissue samples of Hispanic individuals with a pathology-confirmed CRC diagnosis recruited throughout the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). We quantified expression levels of target genes by RT-qPCR normalized with endogenous control GAPDH, using TaqMan Gene Expression Assay in the QuantStudio 3 (Applied Biosystems). Wilcoxon signed-rank test was used to calculate differences between gene expression from tumor and adjacent mucosal tissue samples. Additionally, 39 paired blood and tissue samples were analyzed to explore the association between biomarkers in these two types of samples. Protein biomarkers were measured using a commercially available ELISA kit according to manufacturer protocols (Thermo Scientific Federick, MD and Biosource San Diego, CA). mSEPT9 was measured using the Epi proColon® 2.0 CE test. The association between biomarker presence in tissue and blood samples was assessed using the Chi-square test of independence, with biomarker concentrations dichotomized at the median value. Statistical analyses were performed using Stata 17 and R version 4.3.1. DKK3 and IGFBP2 expression levels were higher among CRC tumor samples. However, expression levels of PKM2 and SEPT9 genes were slightly lower. DKK3 was the only target gene significantly different (p&amp;lt;0.05) when comparing overall gene expression between the matched samples. Upon comparison between early and advanced CRC stages, DKK3 expression levels were higher in advanced-stage tumor samples when compared to adjacent mucosal tissue samples (p&amp;lt;0.05). Moreover, a significant association between IGFBG2 presence in tissue compared to blood was detected at a 90% confidence level (p-value&amp;lt;0.10). This association was evident in early-stage CRC cases; there is a relationship between IGFBG2 biomarker presence in tissue and IGFBG2 biomarker presence in blood (p&amp;lt;0.05). Our findings indicate DKK3 and IGFBP2 as potential biomarkers for CRC progression and early detection. The study’s insights into the differential expression patterns of these biomarkers can inform targeted screening strategies. Further research is needed to assess their potential to enhance early tumor detection in Hispanics. Citation Format: Elba V. Caraballo-Rivera, Hilmaris Centeno-Girona, Gabriel De Jesus-Astacio, Camille Zenon-Melendez, Brenda Torres-Velasquez, Madeline Martir-Ocasio, Marcia R. Cruz-Correa. Differential gene expression of colorectal cancer biomarkers in Hispanic individuals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1024.

The relationship between polymorphism of IGF2BP2 gene rs4402960 and risk of pan-cancer: a meta-analysis and a bioinformatics analysis

Objective To conduct a meta-analysis and a bioinformatics analysis to assess the relationship between IGF2BP2 gene polymorphism and pan-cancer risk. Methods PubMed, EMBASE, and Web of Science were conducted to literature searches. The heterogeneity test was used in five genetic models. Odds ratios (OR), 95% confidence intervals (CI), and p-values were used to evaluate the combined effects of various genetic models. Subgroup analysis and Meta-regression analysis were used to analyze the characteristics of heterogeneity. Sensitivity analysis and publication bias were also performed. Transcriptomic information on IGF2BP2 was downloaded and analyzed from the TCGA and GTEx databases. GEPIA (http://gepia.cancer-pku.cn/) was performed to analyze the relationship between IGF2BP2 expression and cancer tissue. Results This meta-analysis contained 7 case–control studies, with 5,908 cases and 7,890 controls. There were significant differences in the heterozygous genetic model of IGF2BP2 gene rs4402960 polymorphism (OR = 1.080, 95% CI = 1.003–1.163, p = 0.041). In subgroup analysis based on ethnicity, There was a statistical significant association in Chinese (heterozygous: OR = 1.110, 95% CI = 1.010–1.220, p = 0.030). Bioinformatics analysis found that IGF2BP2 was over-expressed in pan-cancer (p < 0.01). In addition, the Kaplan-Meier estimate showed that there is statistical significance of OS between the low and high IGF2BP2 TPM groups in Lung adenocarcinoma (p <0.001). Conclusions To sum up, IGF2BP2 gene polymorphism may be related to cancer risk. IGF2BP2 has diagnostic value in the diagnosis and treatment of pan-cancer.

IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.

Insulin resistance has been correlated with the genetic diversity within the insulin-like binding proteins genes. Moreover, insulin resistance is one of the key characteristics of the widespread reproductive endocrine condition known as polycystic ovarian syndrome (PCOS). Hence, this study is aimed to determine the association between IGFBP3 and IGF2BP2 gene variants and PCOS risk. A total of 300 subjects (150 PCOS cases diagnosed based on Rotterdam ESHRE/ASRM consensus criteria and 150 healthy subjects) were recruited in this case-control cross-sectional study. Tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping rs11705701, whereas genotyping of rs1470579 and rs2854744 was done employing PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The CC and AA+AC genotypes of rs1470579 conferred an increased risk of PCOS in our population. Regarding the rs2854744, an increased risk of PCOS was observed under the codominant homozygous (TT vs. GG) model by 2.54 fold. The C allele of rs1470579 and T allele of rs2854744 enhanced PCOS risk by 1.97 and 1.46 folds, respectively. Haplotype analysis showed that the Ars1470579Ars11705701 haplotype conferred a decreased risk of PCOS (odds ratio = 0.53, 95% confidence interval = 0.34-0.83, p = 0.006). The AC/GG/GT, AA/GA/GT, AC/GA/GG, and AC/GA/GT genotype combinations of rs1470579/rs11705701/rs2854744 were associated with a decreased risk of the disease. IGF2BP2 rs1470579 and IGFBP3 rs2854744 enhanced PCOS susceptibility in a Southeastern Iranian population. Further investigation involving larger cohorts representing diverse ethnic backgrounds is needed to confirm the current findings.

Genome-wide identification of igfbp genes and their different growth expression patterns of mandarin fish

The igfbp family proteins are key regulators of the biological activities of igfs, which play a pivotal role in controlling growth. Growth is highly variable between different fish species and even between growth stages and sexes within the same fish species. For determining the igfbps significantly associated to growth, we identified igfbp genes from the whole-wide genomes of mandarin fish Siniperca chuatsi and big-eye mandarin fish Siniperca kneri, and detected their expression profiles under different growth conditions. The results revealed that: 1) both mandarin fish and big-eye mandarin fish have 10 igfbp family members (igfbp-1a/b, igfbp-2a/b, igfbp-3, igfbp−4, igfbp-5a/b, and igfbp-6a/b), which are highly conserved among igfbp family members; 2) in early development, the expression of igf1 mRNA showed an increasing trend, igfbp-1a/b expression increased significantly with development and the expression trend was strongly similar to that of igf1; 3) variation of body sizes in adult revealed a strong correlation between the serum Gh content and igf1 mRNA expression level in the liver, and the expression levels of hepatic igfbp-2a/b, -4 showed a positive correlation; 4) serum Gh levels and the relative expression of hepatic igf1 mRNA were significantly higher in females than in males, the fold change in igfbp-1a in muscle, -2a, -5a in liver mRNA expression was strongly similar to that of igf1; 5) variation of the interspecific growth showed that the expression of serum Gh and hepatic igf1 mRNA in mandarin fish was significantly higher than that in big-eye mandarin fish. The expression of igfbps mRNA in mandarin fish was significantly higher than that in big-eye mandarin fish, except for igfbp-2a/2b in muscle and igfbp-6a in liver. Taken together, our results suggest that the different effects on growth of mandarin fish are regulated by the actions of different igfbps, where igfbp-1a/b, -2a/b, -4 and -5a may be a candidate for growth rate difference studies. The inherently low expression of Gh, igf1, and igfbps might have contributed to the slow growth of big-eye mandarin fish.

Pan-cancer analysis identified IGF2BP2 as a potential prognostic biomarker for multiple tumor types

BackgroundInsulin-like growth factor 2 (IGF2) mRNA-binding proteins 2 (IGF2BP2/IMP2), an RNA-binding protein encoded by the IGF2BP2 gene, exerts its influence across diverse pathological pathways. While accumulating evidence underscores the potential significance of IGF2BP2 in the tumorigenesis of specific cancers, a comprehensive pan-cancer investigation into its role remains absent.MethodsConsequently, we conducted an exhaustive exploration employing a multitude of databases to elucidate the plausible oncogenic implications of IGF2BP2. This encompassed a comprehensive scrutiny of its expression profiles, prognostic implications, association with cancer-associated fibroblast infiltration, biological functionality in distinct tumor contexts, and plausible correlations with drug sensitivities.ResultsOur findings showed that IGF2BP2 was highly expressed in some types of cancers, but presented at low levels in several cancer types. Furthermore, the role of IGF2BP2 in predicting prognosis exhibited a dichotomous interplay across varied cancer types. Remarkably, observations unveiled the cancer-associated fibroblast infiltration within specific tumors, notably encompassing breast invasive carcinoma of the luminal A subtype, kidney renal clear cell carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, and prostate adenocarcinoma, and thymoma. Intriguingly, gene enrichment analyses spotlighted the co-expression of IGF2BP2 with genes implicated in pivotal biological processes, including DNA replication and recombinational repair.ConclusionOur investigation intricately unveils the potential of IGF2BP2 as a versatile prognostic biomarker across diverse tumor categories. This study bridges existing knowledge gaps and augments the understanding of IGF2BP2’s intricate involvement in tumorigenesis, underscoring its significance as a prospective avenue for therapeutic intervention.

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet.

The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus_sp._CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila, Clostridium_sp._CAG:793, Mycoplasma_sp._CAG:776, Mycoplasma_sp._CAG:472, Clostridium_sp._CAG:609, Akkermansia_sp._KLE1605, Clostridium_sp._CAG:508, and Firmicutes_bacterium_CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1, IGFBP6, and IGFBP4 genes were highly correlated with Clostridium_sp._CAG:793, and Akkermansia_glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity.

Immunomodulatory effects of the induced pluripotent stem cells through expressing IGF-related factors and IL-10 in vitro.

Induced Pluripotent Stem Cells (IPSCs) represent an innovative strategy for addressing challenging diseases, including various rheumatologic conditions. Aside from their regenerative capacities, some studies have shown the potential of these cells in the modulation of inflammatory responses. The underlying mechanisms by which they exert their effects have yet to be fully comprehended. Therefore, we aimed to explore the gene expression linked to the IGF pathway as well as IL-10 and TGF-β, which are known to exert immunomodulatory effects. A C57/Bl6 pregnant mouse was used for obtaining mouse embryonic fibroblasts (MEFs), then the IPSCs were induced using lentiviral vectors expressing the pluripotency genes (OCT4, SOX2, KLF1, and c-MYC). Cells were cultured for 72h in DMEM high glucose plus leukemia inhibitory factor; Evaluating the gene expression was conducted using specific primers for Igf1, Igf2, Igfbp3, Igfbp4, Irs1, Il-10, and Tgf-β genes, as well as SYBR green qPCR master mix. The data were analyzed using the 2-ΔΔCT method and were compared by employing the t test; the results were plotted using GraphPad PRISM software. MEFs were utilized as controls. Gene expression analyses revealed that Igf-1, Igf-bp3, Igf-bp4, and Il-10 were significantly overexpressed (p ≤ .01), while Igf-2 and Tgf-b genes were significantly downregulated in the lysates from IPSCs in comparison with the control MEFs. The Irs1 gene expression was not altered significantly. IPSCs are potentially capable of modulating inflammatory responses through the expression of various anti-inflammatory mediators from the IGF signaling, as well as IL-10. This discovery uncovers a previously unknown dimension of IPSCs' therapeutic effects, potentially leading to more advanced in vivo research and subsequent clinical trials.