Regulating MAPK Signaling Pathway Research Articles

Investigating the attenuating effects of metformin-loaded selenium nanoparticles coupled with Myrtus communis L. flower extract on CaOx deposition in male Sprague Dawley rat kidneys via regulating MAPK signaling pathway

Kidney stones are a foremost clinical concern in urology with CaOx crystals accounting for roughly 80% of these renal formations. This research endeavor seeks to ascertain the protective effects of Metformin-encapsulated selenium nanoparticles (M@Se NPs), combined with a 55% hydroethanolic flower extract from Myrtus communis L. (MCL) in countering the formation of kidney stones in Male Sprague Dawley rats. The particle's diameter was measured to be 39 nm and 13.8 nm from DLS and HR-TEM analysis. Rat groups administered with the MCL-M@Se NPs (1:1.5:1) exhibited reduced renal stone formation in urine and serum analysis compared to the negative control group. Histological evaluations of kidney samples using H&E, and MTS staining indicated a subdued presence of ECM deposition in contrast to other rat groups. Conclusively, the protective mechanism of MCL-M@Se NPs against CaOx stone damage can be confidently attributed to the obstruction of the MAPK signaling pathway.

MiR-290 Family Maintains Pluripotency and Self-Renewal by Regulating MAPK Signaling Pathway in Intermediate Pluripotent Stem Cells.

Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) are derived from pre- and post-implantation embryos, representing the initial "naïve" and final "primed" states of pluripotency, respectively. In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580. The rPSCs exhibited domed clones and expressed key pluripotency genes, with both X chromosomes active in female cells. Furthermore, rPSCs differentiated into cells of all three germ layers in vivo through teratoma formation. Regarding epigenetic modifications, the DNA methylation of Oct4, Sox2, and Nanog promoter regions and the mRNA levels of Dnmt3a, Dnmt3b, and Dnmt1 were reduced in rPSCs compared with EpiSCs. However, the miR-290 family was significantly upregulated in rPSCs. After removing SB203580, an inhibitor of the p38 MAPK pathway, the cell colonies changed from domed to flat, with a significant decrease in the expression of pluripotency genes and the miR-290 family. Conversely, overexpression of pri-miR-290 reversed these changes. In addition, Map2k6 was identified as a direct target gene of miR-291b-3p, indicating that the miR-290 family maintains pluripotency and self-renewal in rPSCs by regulating the MAPK signaling pathway.

Structural characterization, immunomodulatory effect and immune-mediated antitumor activity of a novel polysaccharide from the rhizome of Atractylodis macrocephala Koidz

A novel polysaccharide (WAMPa) was purified from Atractylodis macrocephala Koidz. WAMPa was characterized with molecular weight (MW) distribution, infrared spectrum, monosaccharide composition, methylation and nuclear magnetic resonance spectra. The backbone of WAMPa was → 2)-β-D-Glcp-(1 → interspersed with a small amount of → 5)-α-D-Araf-(1→, and the branches were the terminal α-D-Glcp-(1 → and β-D-Glcp-(1→. The immunomodulatory activities of WAMPa were investigated on two levels experiments including in vitro RAW264.7 cells and in vivo zebrafish. Meanwhile, the immune-mediated antitumor activity was evaluated by the inhibitory effect of the culture medium from WAMPa-treated RAW264.7 cells on human breast cancer cell line MCF-7. Bioactivity assays showed that WAMPa increased mRNA expression levels of TNF-α, IL-6 and iNOS, enhanced the levels of NO, and promoted the phosphorylation of ERK, p38 and JNK. Taken together, these findings revealed that WAMPa exhibited immunomodulatory effects by regulating MAPK signaling pathway. The antitumor experiments showed that WAMPa did not show a significant growth inhibition ratio on MCF-7 cells, but WAMPa-treated RAW264.7 macrophages could significantly inhibit the growth of MCF-7 cells. Thus, the antitumor activity of WAMPa was mediated mainly through the activation of macrophages. These results suggested that WAMPa could be considered as potential immunomodulatory and antitumor supplements.

β-eudesmol inhibits cell proliferation and induces ferroptosis via regulating MAPK signaling pathway in breast cancer

The aim of this study was to explore the influences and underlying mechanisms of β-eudesmol on breast cancer (BC). Different concentrations of β-eudesmol (0, 10, 20, and 40 μM) were taken to treat BC cells. Cell Counting Kit-8, colony formation assay, and flow cytometry were performed to evaluate the influences of β-eudesmol on cell viability, proliferation, and apoptosis. To assess the influences of β-eudesmol on cell ferroptosis, the change of ROS, SOD, MDA, and intracellular iron and Fe2+ were determined. The protein changes of apoptosis, ferroptosis, and MAPK pathway (Bcl-2, Bax, cleaved caspase-3, SLC7A11, GPX4, SLC40A1, Transferrin, MEK1, and ERK1/2) were checked utilizing Western blot. In a concentration-dependent manner, β-eudesmol restrained cell viability and proliferation. β-eudesmol promoted cell apoptosis, as evidenced by the decline level of Bcl-2 and the raised level of Bax and cleaved caspase-3. β-eudesmol enhanced the level of ROS, MDA, iron, Fe2+, and Transferrin, and lessened SOD activity and the protein expression of SLC7A11, GPX4, SLC40A1, MEK1, and ERK1/2. Moreover, ferroptosis inhibitor Fer-1 and MEK1 overexpression both reversed the changes on cell proliferation, apoptosis, and ferroptosis induced by β-eudesmol. β-eudesmol inhibited cell proliferation and promoted cell apoptosis and ferroptosis via regulating MAPK pathway in BC.

ANKRD29, as a new prognostic and immunological biomarker of non–small cell lung cancer, inhibits cell growth and migration by regulating MAPK signaling pathway

BackgroundThe predominant cancer-related deaths worldwide are caused by lung cancer, particularly non-small cell lung cancer (NSCLC), despite the fact that numerous therapeutic initiatives have been devised to improve the outcomes. Ankyrin repeat domain (ANKRD) is one of the widespread protein structural motifs in eukaryotes but the functions of ANKRD proteins in NSCLC progression remains unclear.MethodsWe performed integrative bioinformatical analysis to determine the dysregulated expression of ANKRDs in multiple tumors and the association between ANKRD29 expression and the NSCLC tumor environment. Quantitative real-time PCR (qRT-PCR), western blot, immunohistochemistry (IHC), and tissue microarray (TMA) assays were used to investigate the expression of ANKRD29 in NSCLC cell lines. The role of ANKRD29 in NSCLC cell proliferation and migration in vitro was deteceted by 5-bromodeoxyuridine (BrdU) incorporation, colony formation, flow cytometry, would-healing, trans-well, and western blot experiment. RNA-seq technology was applied to deciper the molecular mechanism regulated by ANKRD29 in NSCLC.ResultsWe constructed a valuable risk-score system for predicting the overall survival outcomes of NSCLC patients based on the expression of five hub ANKRD genes. And we found that the hub gene ANKRD29 was remarkedly decreased in NSCLC tissues and cell lines due to the promoter hypermethylation, and revealed that high ANKRD29 expression obviously correlated with patients’ better clinical outcome. Overexpression of ANKRD29 significantly inhibited cell proliferation and migration, promoted the cancerous cells’ sensitivity to carboplatin and enhanced the killing ability of T cells in NSCLC cells. Interestingly, ANKRD29 can be served as a biomarker to predict the response to immunotherapy in NSCLC. Mechanically, RNA-seq results showed that ANKRD29 could regulate MAPK signaling pathway. Moreover, we screened two potential agonists for ANKRD29.ConclusionsANKRD29 functions as a new tumor suppressor in NSCLC tumorigenesis and could be developed as a biomarker for prognostic prediction, immunotherapy response, and drug susceptibility evaluation of NSCLC in the future.

LncRNA LOXL1-AS1 promotes proliferation and invasion and inhibits apoptosis in retinoblastoma by regulating the MAPK signaling pathway.

Retinoblastoma (RB) is an intraocular malignancy that is most common in children and rare in adults. Addressing novel biomarkers and therapeutic targets for RB to modulate tumor progression has become a challenge. The aim of the present study was to investigate the function of long non-coding RNAs (LncRNAs) LOXL1-AS1 in RB cell proliferation and metastasis. It was found that LOXL1-AS1 was overexpressed in RB tissues and cells. In order to evaluate cell viability and colony formation potential, the knockdown of LOXL1-AS1 has been established. Knockdown of LOXL1-AS1 was also inhibited cells migration and invasion. In addition, the proportion of cells in the G2/M phase of the sh-LOXL1-AS1 group increased significantly, and the proportion of cells in the sh-NC group decreased significantly. In the xenograft model of RB, the tumors in the sh-LOXL1-AS1 group grow slowly compared to the sh-NC group. Western blot analysis revealed that LOXL1-AS1 can regulate the progression of RB cells through MAPK signaling pathway in vitro and in vivo. These results indicated that LncRNA LOXL1-AS1 promotes proliferation, invasion and inhibits apoptosis of retinoblastoma by regulating MAPK signaling pathway, and might be expected to be a novel basis for clinical diagnosis and treatment.

Extract of Styrax japonica attenuates glutamate-induced apoptosis via regulating MAPK signaling pathway in HT22 hippocampal cells

Two-thirds of people with dementia suffer from Alzheimer’s disease, and there is a need to develop treatments with fewer side effects. Cholinergic and glutamate-induced brain damage occurs in the early stages of Alzheimer’s disease, so substances that suppress these symptoms may be potential candidates for the treatment. Ethanol extracts of 40 kinds of oriental medicine plants were examined whether they have acetylcholine esterase (Ache) inhibitory properties. We next investigated whether the ethanol extracts of six oriental medicine plants showing Ache inhibitory activity could inhibit glutamate-induced HT22 cell death. The ethanol extract of Styrax japonica (EESJ) was found to be relatively superior in both inhibitory activities. MTT and annexin V/PI staining assays confirmed that EESJ inhibited glutamate-induced apoptosis in the HT22 mouse hippocampal cells. EESJ also suppressed glutamate-mediated ROS production and attenuated the phosphorylation levels of MAPK members including ERK, JNK, and p38 kinases. Therefore, EESJ is a suitable candidate for developing a substance of Alzheimer’s disease treatment.

Scoparone inhibits the growth of liver cancer cells by regulating MAPK signaling pathway

Purpose: To investigate the possible effects of scoparone on the viability, apoptosis and motility of liver cancer cells, as well as the mechanism of action. 
 Methods: CCK-8 and colony formation assays were carried out to determine liver cancer cell viability, while flow cytometry (FCM) and Immunoblot assays were performed to evaluate cell apoptosis. Wound closure and Transwell assays were performed to determine the effect of scoparone on cell motility, while immunoblot assays were performed to assess the effect of the compound on MAPK pathway of liver cancer cells. 
 Results: Scoparone suppressed the viability of Hep3B2 and Huh-7 cells (p < 0.01), as well as the apoptosis and motility of the cells (p < 0.01). Furthermore, scoparone inhibited the growth of liver cancer cells via MAPK pathway. 
 Conclusion: Scoparone suppresses liver cancer cell growth via MAPK pathway, and is thus a promising drug for liver cancer treatment. However, in vivo studies are required to validate these findings.

Comprehensive analysis of transcriptome-wide m6A methylome in the lung tissues of mice with acute particulate matter exposure

Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The m6A methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the m6A methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated m6A peaks within 1879 genes and 1278 differentially hypomethylated m6A peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four m6A-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the m6A-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.

The exon 12-containing LHX6 isoforms promote cervical cancer cell proliferation by regulating the MAPK signaling pathway.

LIM homeobox 6 (LHX6) has been reported to be downregulated and inhibits cell proliferation in various cancers. Alternative splicing of LHX6 leads to six annotated isoforms, which can be found in the NCBI database. However, the expression patterns and potential roles of these isoforms remain poorly characterized in cervical cancer. Here, we demonstrated that the LHX6 isoforms containing exon 12 (LHX6EX(+12) group) and isoforms lacking exon 12 (LHX6EX(–12) group) were differentially expressed in cervical tissue by qRT‐PCR. The mRNA expression level of LHX6EX(+12) group was higher than that of LHX6EX(−12) group in cervical cancer tissue. Knockdown of LHX6EX(+12) group and all LHX6 isoforms (LHX6All group) inhibited cell growth, increased cell apoptosis, and induced cell cycle arrest from G0/G1 phase to S phase in vitro. Consistently, overexpression of the LHX6EX(+12) group promoted cervical cancer cell proliferation in vitro. In contrast, no significant differences in cell proliferation were found between LHX6EX(−12) isoform knockdown group and its control. RNA‐sequencing suggested that the LHX6EX(+12) isoform group might exert its cancer‐promoting effects in cervical cancer via regulating MAPK signaling pathway. Downregulation of the LHX6EX(+12) group significantly suppressed the phosphorylation of MRK, ERK, JNK, and P38 at the protein level. We also identified some unique biological processes and signaling pathways in which each isoform group might be involved. In summary, our results indicated that LHX6EX(+12) isoform group was the dominant oncogenic type of LHX6 in cervical cancer, which may be a new biomarker and a potential precise therapeutic target for cervical cancer in the future.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats

Ethnopharmacological relevanceTraditional herb couple Angelicae pubescentis radix (APR) and Notopterygii rhizoma et radix (NRR), composition of two traditional Chinese medicinal herbs, has been used clinically in China for the treatment of rheumatoid arthritis (RA) over years. APR and NRR contain coumarins and phenolic acids, which have been reported to have analgesic and anti-inflammatory activities. Aim of the studyThe active ingredients combination (AIC) and potential therapeutic mechanism of APR and NRR (AN) herb couple remain unclear. Therefore, the present study aimed to identify the AIC and elucidate the underlying mechanism of AIC on RA. Materials and methodsFirstly, a novel strategy of in vitro experiments, computational analysis, UPLC-QTOF-MS and UPLC-QQQ-MS was established to confirm the optimum ratio of AN herb couple samples and identified the AIC. Then, the anti-arthritis effects of the optimal herb couple and AIC were studied with Collagen II induced rheumatoid arthritis (CIA) rats in vivo. Finally, an integrated model of network pharmacology, metabolomics, gut microbiota analysis and biological techniques were applied to clarify the underlying mechanism through a comprehensive perspective. ResultsAN7:3 herb couple was regarded as the optimal ratio of AN herbal samples, and AIC was screened as osthole, columbianadin, notopterol, isoimperatorin, psoralen, xanthotoxin, bergapten, nodakenin and bergaptol respectively. Additionally, AIC exerted similar therapeutic effects as AN 7:3 in CIA rats. Moreover, AIC ameliorated RA might via regulating MAPK signaling pathway, altering metabolic disorders and gut microbiome involved autoimmunity. Conclusionsour findings provided scientific evidence to support that AIC of AN herb couple could be used as a prebiotic agent for RA. Importantly, this research provided a systematic and feasible strategy to optimize the proportion of medicinal materials and screen AIC from multi-component traditional Chinese herb couples or Chinese medicine formulae. Moreover, it provided a comprehensive perspective to discover AIC, clarify the overall effects and understand the mechanisms for natural products through the perspective of database and multi-omics integration.

Research progress of traditional Chinese medicine monomers in intervening colorectal cancer by regulating MAPK signaling pathway

Research progress of traditional Chinese medicine monomers in intervening colorectal cancer by regulating MAPK signaling pathway

GINS2 affects cell proliferation, apoptosis, migration and invasion in thyroid cancer via regulating MAPK signaling pathway.

Globally, thyroid cancer (TC) is considered to be the commonest endocrine malignancy. GINS complex subunit 2 (GINS2) belongs to the GINS complex family and is associated with cellular migration, invasion and growth. The present study aimed to investigate the underlying mechanisms of GINS2 on cell viability, migration and invasion in TC cells. By using MTT, wound healing and Transwell assays, the cell viability, migration and invasion were determined. Apoptosis was examined by immunofluorescence. Western blotting was used to detect protein expression levels. In the present study, biological function analysis demonstrated that GINS2 interference attenuated cell viability, migration and invasion in TC cell lines (K1 and SW579). It was discovered that, compared with the control group, GINS2 silencing induced apoptosis in TC cells. Additionally, GINS2 interference inhibited key proteins in the MAPK signaling pathway, including JNK, ERK and p38. According to these comparative experiments, GINS2 was considered to act a pivotal part in cell viability, migration and invasion of TC by regulating the MAPK signaling pathway and might be a potential therapeutic target for treating TC.

Imperatorin reduces the inflammatory response of atherosclerosis by regulating MAPKs signaling pathway in vivo and in vitro

Inflammation plays an important role in the process of atherosclerosis (AS). Inhibition of inflammation is an effective way to prevent AS. Imperatorin (IMP) is a kind of furan coumarin with various activities. In this study, the anti-inflammatory effect of IMP was explored in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs and high fat diet (HFD)-induced ApoE-/- mice. The results showed that IMP attenuated the elevation of TNF-α, IL-6, MCP-1 and NO induced by ox-LDL in supernatant of VSMCs. IMP has normalized the levels of serum lipids (TC, TG, LDL-C and HDL-C) and attenuated inflammatory cytokines in serum. IMP also improved pathological changes and lipid accumulation in aorta. Matrix metalloproteinase-2 (MMP-2) expression in aorta was down-regulated by IMP. IMP could inhibit the phosphorylation of MAPKs pathway in the aorta and VSMCs, resulting in a significant decrease in the contents of p-ERK 1/2, p-JNK and p-P38. Overall, IMP could exert anti-inflammatory effects in vivo and in vitro to interfere with AS.

Up-regulation of C5orf34 promotes lung adenocarcinoma migration and is correlated with worse prognosis

ObjectiveThis study aimed to investigate the biological role of C5orf34 in Lung adenocarcinoma (LAD) and the mechanism of such role. MethodsThe mRNA expression of C5orf34 was analyzed using student's t-test based on the data obtained from TCGA database. Kaplan-Meier analysis was performed to evaluate the prognosis value of C5orf34. Chi-square (χ2) test was performed to analyze the correlation between C5orf34 expression and clinical features. The effect of C5orf34 siRNA on A549 and SPCA1 cells proliferation and migration were explored using CCK8 assay, wound healing assay and transwell assays, respectively. Western blot was performed to evaluate the expression of C5orf34, ERK, p-ERK, MEK and p-MEK. ResultsC5orf34 expression was enhanced in LAD and positively correlated with poor prognosis in patients with LAD. χ2 test revealed that C5orf34 expression was obviously associated with age (p = 0.016), Pathologic-Stage (p = 0.045) and Pathologic-N (p = 0.023). In addition, knockdown of C5orf34 significantly suppressed A549 and SPCA1 cells proliferation and motility (p < 0.01) in vitro. Moreover, by western blot analysis, we found that depleting C5orf34 remarkably reduced the ratio of p-MEK/MEK and p-ERK/ERK in A549 cells. ConclusionOur results firstly revealed that C5orf34 might play a facilitating role in LAD development and progression by regulating MAPK signaling pathway. Furthermore, our data implied that C5orf34 may be a potential predictor and treatment target for LAD.

HCC Specific Protein Network Involving Interactions of EGFR with A-Raf and Transthyretin: Experimental Analysis and Computational Biology Correlates.

The network interactions link human disease proteins to regulatory cellular pathways leading to better understanding of protein functions and cellular processes. Revealing the network of signaling pathways in cancer through protein-protein interactions at molecular level enhances our understanding of Hepatocellular Carcinoma (HCC). A rodent model for study of HCC was developed to identify differentially expressed proteins at very early stage of cancer initiation and throughout its progression. HCC was induced by administrating N-Nitrosodiethylamine (DEN) and 2-aminoacetylfluorine (2-AAF) to male Wistar rats. Proteomic approaches such as 2D-Electrophoresis, PD-Quest, MALDI-TOF-MS and Western blot analyses have been used to identify, characterize and validate the differentially expressed proteins in HCC-bearing animals vis-a-vis controls. The step-wise analysis of morphological and histological parameters revealed HCC induction and tumorigenesis at 1 and 4 months after carcinogen treatment, respectively. We report a novel protein network of 735 different proteins out of which eight proteins are characterized by MALDI-TOF-MS analysis soon after HCC was chemically induced in rats. We have analyzed four different novel routes representing the association of experimentally identified proteins with HCC progression. The study suggests that A-Raf, transthyretin and epidermal growth factor receptor play major role in HCC progression by regulating MAPK signaling pathway and lipid metabolism leading to continuous proliferation, neoplastic transformation and tumorigenesis.

Chrysin promotes SMMC-7721 cell apoptosis by regulating MAPKs signaling pathway

To study the effect of chrysin in inducing apoptosis of human hepatic carcinoma cells and explore the possible mechanism. Human hepatic carcinoma SMMC-7721 cells treated with DMSO or chrysin at different concentrations (5-200 μg/mL) were examined for changes in the cell proliferation using CCK-8 assay. The morphological changes of SMMC-7721 cells were observed in response to treatment with 5, 10, or 20 μg/mL chrysin, and the changes in the cell nuclei were observed using DAPI nuclear staining. Annexin Ⅴ-FITC/PI flow cytometry was used to determine the cell apoptosis rate. The changes in the apoptosis-related proteins (PARP and caspase-3) and MAPKs signal pathway were detected with Western blotting. Chrysin treatment obviously suppressed the proliferation of SMMC-7721 cells in a dose-dependent manner below the concentration of 60 μg/mL. Chrysin (20 μg/mL) also caused significantly increased cell apoptosis and significant cleavage of PARP and caspase-3. Chrysin significantly activated MAPKs signaling pathway in a time-and dose-dependent manner, with the peak activation level occurring at 15 min. Pretreatment of the cells with specific inhibitors of the MAPKs pathway obviously inhibited the effect of chrysin in inducing cell apoptosis. Chrysin inhibits the proliferation and promotes apoptosis of SMMC-7721 cells by regulating the activation of MAPKs signaling.

MicroRNA-4728 mediated regulation of MAPK oncogenic signaling in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer that accounts for 85% of thyroid cancers. MicroRNAs (miRNAs) have been reported to play important roles in the biological processes in cancer. In this study, we analyzed the biological role of miR-4728 in human PTC process in human PTC cell lines in vitro. MiRNA-4728 was observed to down-regulated in human PTC tissues and PTC cell lines. Additionally, miR-4728 inhibited PTC cell proliferation. Further study demonstrated SOS1 was repressed by miR-4728 and overexpression of miR-4728 down-regulated both the mRNA and protein levels of SOS1. Moreover, miR-4728 overexpression also decreased the MAPK signaling activity. These observations suggested that miR-4728 could inhibit the process of human PTC through regulating MAPK signaling pathway. And, appropriate regulation of miR-4728 might be vital to improve human PTC treatment.

Overexpression of COL3A1 confers a poor prognosis in human bladder cancer identified by co-expression analysis.

Human bladder cancer (BCa) is one of the worldwide cancers in men and women populations, with the etiology and mechanism unknown. In our study, we constructed a weighted gene co-expression network to identify gene modules associated with the progression of BCa (n = 93). In the significant module (R2 = 0.48), a total of 103 network hub genes were identified, and 4 of them were hub nodes in the protein-protein interaction network as well. In validation, COL3A1 showed a higher correlation with the disease progression than any other hub genes in hub module in the test set (p < 0.001). Functional and pathway enrichment analysis demonstrated that COL3A1 is overrepresented in pathway of focal adhesion, which associated with tumor progression and might cause metastasis. Gene set enrichment analysis (GSEA) also demonstrated that the gene set of “MAPK signaling pathway” and focal adhesion related pathways were enriched in BCa samples with COL3A1 highly expressed (FDR < 0.05). Considering the clinicopathological parameters, highly-expressed COL3A1 was closely correlated with local recurrence and BCa stage. Survival analysis revealed that BCa patients with higher expression of COL3A1 had a significantly shorter overall survival time and disease free survival time.In conclusion, based on the co-expression analysis, COL3A1 was identified in the association with progression and prognosis of BCa, which might refer a poor prognosisprobably by regulating MAPK signaling pathway.

MiRNA-106a directly targeting RARB associates with the expression of Na(+)/I(-) symporter in thyroid cancer by regulating MAPK signaling pathway.

BackgroundSerum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed. These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated.MethodsExpression levels of six identified miRNAs were assessed via quantitative real-time PCR (qRT-PCR) in the serum of eligible patients. Dual-luciferase reporter assay was used to determine the potential target of miR-106a. Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The change of gene expression was detected by qRT-PCR and western blotting analysis. In vitro iodine uptake assay was conducted by a γ-counter.ResultsCompared to PTC patients with 131I-avid lung metastases, miR-106a was up-regulated in the serum of patients with non-131I-avid lung metastases. The results of dual-luciferase reporter assay demonstrated that miR-106a directly targeted retinoic acid receptor beta (RARB) 3′-UTR. miR-106a-RARB promoted viability of thyroid cancer cells by regulating MEKK2-ERK1/2 and MEKK2-ERK5 pathway. miR-106a-RARB inhibited apoptosis of thyroid cancer cells by regulating ASK1-p38 pathway. Moreover, miR-106a-RARB could regulate the expression of sodium iodide symporter, TSH receptor and alter the iodine uptake function of thyroid cancer cells.ConclusionsmiRNA-106a, directly targeting RARB, associates with the viability, apoptosis, differentiation and the iodine uptake function of thyroid cancer cell lines by regulating MAPK signaling pathway in vitro. These findings in the present study may provide new strategies for the diagnosis and treatment in radioiodine-refractory differentiated thyroid carcinoma.