miR-155 Research Articles

MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4.

The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated. The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system. In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253. Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

Abstract 16391: Pro-Neoplastic Properties of Small Extracellular Vesicles From Failing Hearts

Background: Heart diseases are associated with an increased incidence of cancer independently of shared risk factors. The mechanism beyond this link is complex, unclear and limits our ability to develop effective therapies. We aimed to test the hypothesis that small cardiac extracellular vesicles (sEVs) contribute to the link between HF and cancer. Methods & Results: We used mouse models of heterotopic and orthotopic lung cancer and post-myocardial infarction (MI) heart failure (HF). sEVs were isolated by size exclusion chromatography. To determine the role of cardiac EVs in tumor growth, we focused on sEVs from cardiac mesenchymal stromal cells (cMSCs). cMSCs after MI secreted twice more sEVs, characterized with a unique proteome, compared with cMSCs from sham-MI ( Fig 1A ). cMSC-sEVs from post-MI HF harbored more tumor-promoting cytokines and microRNA (miR), such as periostin, osteopontin, IL-6, TNFα, galectin-3, and miR's 221 and 21. The pro-neoplastic effects of cMSC-sEVs on cancer cells were depended on cancer type, with a marked increase in proliferation and migration of lung and colon cancer cells but only a modest increase with more malignant triple-negative breast and melanoma cancer cells. Next, we inoculated lung cancer cells into mice and found that post-MI HF accelerated tumor growth. Furthermore, adoptive transfer of cMSC-sEVs from failing hearts accelerated tumor growth with and without systemic EV depletion ( Fig 1B ). Finally, we found that spironolactone mitigated the neoplastic effects of HF, attenuated tumor growth ( Fig 1C ), and reduced the number of cMSC-sEVs by 26%. Conclusions: We show, for the first time, that cardiac extracellular vesicles from post-MI failing heart harbor pro-neoplastic properties and promote tumor growth independently of other secreted factors. Spironolactone reduces the number of cardiac extracellular vesicles and the pro-neoplastic effects of post-MI heart failure.

Diosgenin inhibits the proliferation and migration of MCF-7 breast cancer cells through the demethylation of miR-145 gene.

Diosgenin inhibits the proliferation and migration of MCF-7 breast cancer cells through the demethylation of miR-145 gene.

Оценка метилирования генов MIR-143 и MIR-145 в лимфоузлах больных диффузной В-крупноклеточной лимфомой

Introduction. The expression of miR-143 and miR-145 oncosuppressive microRNAs is observed in all types of normal tissues studied and, according to numerous studies, it is lost in malignant neoplasms. A decrease in the expression of these microRNAs in diffuse large B-cell lymphoma (DLBCL) is described, the mechanisms of which require additional study. Aim. To evaluate the methylation of MIR-143 and MIR-145 genes in the lymph node tissue of patients with DLBCL and lymph nodes of patients with reactive follicular hyperplasia. Materials and methods. The study included biopsies of 14 formalin-fixed and paraffinized tumor lymph nodes of patients with DLBCL and 11 lymph nodes of patients with reactive lymphadenopathy. The methylation status of the MIR-145 gene in samples was determined by the method of methyl-specific polymerase chain reaction. Direct bisulfite sequencing based on the Sanger method was used to quantify the methylation of the MIR-143 gene. Results. It was found that all the studied samples, both reactive and tumor, had methylation of the MIR-145 gene. A similar level of methylation of CpG dinucleotides of the MIR-143 gene was registered in all samples of reactive lymph node tissue, whereas tumor samples showed greater heterogeneity. In the samples of DLBCL, namely a non-germinal B cell phenotype, the average level of methylation of the studied fragment of the MIR-143 gene sequence was significantly lower, than in the samples of reactive lymph nodes (p = 0.026). Conclusion. The methylation of MIR-143 and MIR-145 genes detected in the lymph nodes of patients with DLBCL is not tumor-specific. The complex cellular composition of the analyzed samples, as well as the different density of microvessels, may explain the differences in the level of MIR-143 methylation in the tissue of reactive and tumor lymph nodes.

Genetic variants in miR-145 gene are associated with the risk of asthma in Taiwan

Asthma is a chronic airway inflammation disease and the diagnosis and treatment strategies remain difficult. MicroRNAs play important roles in many biological and pathological processes including asthma development. There is no study confirming the contribution of genetic variants in miR-145 to asthma etiology. We hypothesize that single nucleotide polymorphisms (SNPs) in the promoter region of miR-145 may be associated with the risk of asthma in Taiwanese. We used a case–control study to test this hypothesis. In 198 asthma patients and 453 healthy controls, the genotypes of miR-145 rs4705342 and rs4705343 were determined, and the associations of miR-145 genotypes with asthma risk and severity were evaluated. The distribution of miR-145 rs4705342 genotypes between asthma patients and non-asthmatic control groups were significantly different (p = 0.0187). In multivariable logistic regression analysis, compared with the wild-type TT genotype, individuals carrying the variant genotypes had progressively decreased risks of asthma: the odds ratio (OR) for the heterogeneous variant genotype (CT) and homozygous variant genotype (CC) was 0.77 (95% CI 0.55–1.10, p = 0.1788) and 0.41 (95% CI 0.21–0.79, p = 0.0102), respectively (p for trend = 0.0187). In allelic test, the C allele was associated with a 31% reduced risk of asthma (OR = 0.69, 95% CI 0.53–0.90, p = 0.0070). In addition, the rs4705342 variant genotypes were correlated with the symptom severity (p = 3 × 10–5). Furthermore, the variant genotypes correlated with lower miR-145-5p expression level in serum (p = 0.0001). As for rs4705343, there was no differential distribution of genotypes between cases and controls. Our data provide evidence for miR-145 rs4705342 to serve as a novel biomarker for asthma risk prediction.

Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival.

Background: There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA–microRNA (miRNA) binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC. Methods: We conducted a case–control study of 507 patients with CRC recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′UTR) with susceptibility to CRC and patients’ survival. In addition, genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′UTR of KRAS were selected for analysis using the Haploview and HaploReg software. Results: Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent non-neoplastic large intestinal mucosa. The rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with susceptibility to CRC (adjusted odds ratio (OR): 2.414, 95% CI: 1.385–4.206). Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). Patients having CRC carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio (HR): 4.328, 95% CI: 1.236–15.147). Conclusions: Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for susceptibility to CRC and patients’ survival.

Expression and effect of microRNA-205 in hypertrophic scar

Objective: To investigate the expression and effect of microRNA-205 (miR-205) in hypertrophic scar. Methods: The experimental research method were applied. From October 2019 to January 2020, hypertrophic scar tissue from 6 patients with hypertrophic scar [1 male and 5 females, aged (36±7) years], and remaining normal skin tissue from 6 trauma patients [2 males and 4 females, aged (38±9) years] after flap transplantation operation were collected. The above-mentioned 12 patients were admitted to the General Hospital of Northern Theater Command and met the inclusion criteria. Real time fluorescent quantitative polymerase chain reaction was used to detect the mRNA expressions of miR-205 and thrombospondin-1 (TSP-1). The hypertrophic scar tissue was taken to culture the 3rd to 5th passage of fibroblasts (Fbs) for the follow-up experiments. Fbs of hypertrophic scar was divided into TSP-1+miR-205 control group, TSP-1+miR-205 mimic group, TSP-1 mutant+miR-205 control group, TSP-1 mutant +miR-205 mimic group, which were transfected with the corresponding sequences. At 48 h after transfection, the expressions of luciferase and renal luciferase were detected by luciferase reporter gene detection kit, and the luciferase/renal luciferase ratio was calculated to indicate the activity of TSP-1. Two batches of hypertrophic scar Fbs were collected and divided into miR-205 control group, miR-205 mimic group, and miR-205 inhibitor group and miR-205 control group, miR-205 mimic group, and miR-205 mimic+TSP-1 group, respectively, which were transfected with the corresponding sequences. At 0 (immediately), 12, 24, 36, and 48 h after transfection, the cell viability was detected by microplate reader. Two batches of hypertrophic scar Fbs were collected, grouped, and treated as the cell viability detecting experiment. At 24 h after transfection, Hoechst 33258 staining was performed to observe the nuclear shrinkage, so as to reflect the apoptosis of Fbs. The number of samples in cell experiment was 3. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and t test. Results: The mRNA expression of miR-205 in hypertrophic scar tissue was 0.54±0.05, which was significantly lower than 1.26±0.07 in normal skin tissue (t=8.213, P<0.01). The expression of TSP-1 mRNA in hypertrophic scar tissue was 1.46±0.07, which was significantly higher than 0.68±0.11 in normal skin tissue (t=6.031, P<0.01). At 48 h after transfection, the luciferase/renal luciferase ratio reflecting the TSP-1 activity of cells in TSP-1+miR-205 mimic group was 0.532±0.028, which was significantly lower than 0.998±0.012 in TSP-1+miR-205 control group (t=26.500, P<0.01), and the luciferase/renal luciferase ratio of cells in TSP-1 mutant+miR-205 mimic group was 0.963±0.012, which was close to 0.976±0.010 in TSP-1 mutant+miR-205 control group (t=0.816, P>0.05). At 12, 24, 36, and 48 h after transfection, the cell viability in miR-205 mimic group was significantly lower than that in miR-205 control group (t=6.169, 12.670, 27.130, 12.670, P<0.05 or P<0.01). At 0, 12, 24, 36, and 48 h after transfection, the cell viability in miR-205 inhibitor group was significantly higher than that in miR-205 control group (t=6.169, 7.221, 7.787, 7.835, 13.030, P<0.05 or P<0.01). At 12, 24, 36, and 48 h after transfection, the cell viability in miR-205 mimic group was significantly lower than that in miR-205 control group and miR-205 mimic+TSP-1 group (t=8.118, 26.970, 39.550, 42.490, 14.570, 12.240, 36.830, 45.220, P<0.05 or P<0.01). At 24 h after transfection, compared with miR-205 control group, the cell apoptosis in miR-205 mimic group was increased, and the cell apoptosis in miR-205 inhibitor group was decreased. At 24 h after transfection, compared with miR-205 mimic group, the cell apoptosis in miR-205 control group miR-205 mimic+TSP-1 group were decreased. Conclusions: miR-205 can inhibit the proliferation and promote the apoptosis of Fbs in hypertrophic scar by inhibiting the expression of TSP-1, which has the potential to be the therapeutic target for hypertrophic scar.

MicroRNAs as biomarkers for breast cancer.

Breast cancer is one of the most common cancers among women and is the second leading cause of cancer-related deaths. Mammography is currently the gold standard diagnostic tool however it is not without limitations. Over the past decade, research has largely shifted focus from mRNA biomarkers to microRNAs (miRNAs) as a new potential screening biomarker for breast cancer. MiRNAs are 18–25-nucleotides regulatory non-coding RNA molecules that regulate the expressions of a wide variety of genes have crucial roles in many areas from organogenesis to carcinogenesis. This study was conducted to investigate miR 21, miR 27b, miR 125a, miR 155, miR 200c, miR 335, and miR373 in 20 patients with breast cancer patients. 20 healthy women served as controls. microRNAs were assessed using Real Time PCR method. Three microRNAs (miR 21, miR155 and miR125) were found to be significantly more abundant in the plasma of early-stage breast cancer (ESBC) patients compared to controls. Therefore, these 3 microRNAs could represent a promising circulating biomarker candidate for the ESBC diagnosis if the results will be validated in a wider group of patients. (www.actabiomedica.it)

MiR-155 regulates the proliferation and apoptosis of pancreatic cancer cells through targeting SOCS3.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 regulates the proliferation and apoptosis of pancreatic cancer cells through targeting SOCS3, by J. Wang, J. Guo, H. Fan, published in Eur Rev Med Pharmacol Sci 2019; 23 (12): 5168-5175-DOI: 10.26355/eurrev_201906_18181-PMID: 31298410" has been withdrawn. The authors stated that the problem was related to "substantial deficiency in the experimental design (Figures 3B and 4C, 4E, and 4F). The experiment was not done well at that time. It was processed by computer and there were some inaccuracies". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18181.

Retraction: Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation.

[This corrects the article DOI: 10.4103/1673-5374.290908].

MiR-144 inhibits colorectal cancer cell migration and invasion by regulating PBX3.

MicroRNAs (miRNA) are aberrantly expressed in various human cancers, including colorectal cancer (CRC). We aim to investigate the functional role and underlying mechanism of miR-144 in CRC. The expressional level of miR-144 and pre-leukemia transcription factor 3 (PBX3) in CRC tissues and cells was confirmed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. The migration and invasion of CRC cells were detected by transwell assay. Luciferase reporter assay was performed to determine the specific target of miR-144 in CRC cells. The results displayed that miR-144 expression was significantly decreased in CRC tissues and cells compared to that in normal controls. Additionally, miR-144 mimic suppressed, while miR-144 inhibitor promoted the ability of CRC cell migration and invasion. More importantly, PBX3 was the direct target of miR-144 in regulating CRC development and PBX3 could reverse the inhibitory effect of miR-144 mimic on CRC cells. PBX3 expression was significantly increased in CRC and negatively correlated with miR-144 expression. In conclusion, miR-144 suppressed CRC cell migration and invasion by targeting PBX3, suggesting its potential value in the diagnosis and treatment of CRC.

Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA ZFPM2-AS1 promotes the tumorigenesis of renal cell cancer via targeting miR-137, by J.-G. Liu, H.-B. Wang, G. Wan, M.-Z. Yang, X.-J. Jiang, J.-Y. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5675-5681-DOI: 10.26355/eurrev_201907_18304-PMID: 31298319" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18304.

Circular RNA circ_0017247 promotes melanoma migration and invasion via targeting miR-145.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ_0017247 promotes melanoma migration and invasion via targeting miR-145, by Z. Chen, K. Kang, S. Chen, S. Wang, J. Zhang, X.-Y. Zhang, Z. Chen, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1932-1938-DOI: 10.26355/eurrev_202002_20371-PMID: 32141562" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20371.

MiR-145 targeting BNIP3 reduces apoptosis of chondrocytes in osteoarthritis through Notch signaling pathway.

The purpose of this study was to explore the effect of micro ribonucleic acid (miR)-145 on the apoptosis of chondrocytes in osteoarthritis (OA), and to research the association between its targeting on B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) and Notch signaling pathway and chondrocyte apoptosis. The mouse model of OA was established via surgery, and chondrocytes were isolated and cultured in vitro. Then, the chondrocytes were transfected with miR-145 inhibitor, miR-145 mimics, miR-negative control (NC), BNIP3-siRNA and BNIP3-vector, respectively, with those normally cultured as the control. After that, the expression levels of miR-145 and BNIP3 in cells were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the apoptosis rate was detected via flow cytometry, and the apoptosis level was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the target gene sequences were predicted and compared using the software, and the BNIP3 Luciferase reporter vectors containing predicted target sites for miR-145 were constructed. Finally, the protein expressions of BNIP3, Notch1, and P21 were determined through Western blotting. The results of qRT-PCR showed that in OA chondrocytes, the expression of miR-145 was lower than that in normal chondrocytes (p<0.05), while the mRNA and protein expressions of BNIP3 were higher than those in normal chondrocytes (p<0.05). According to flow cytometry, the apoptosis rate was (4.4±0.6)% in normal cartilage tissues and (29.2±2.1)% in OA cartilage tissues. Overexpression of miR-145 significantly reduced chondrocyte apoptosis (p<0.05), while overexpression of BNIP3 markedly increased chondrocyte apoptosis (p<0.05). In addition, the Luciferase reporter system showed that miR-145 mimics evidently inhibited BNIP3 (p<0.05) and suppressed the Notch signaling pathway (p<0.05), while BNIP3 enhanced the expression of Notch signaling pathway (p<0.05). MiR-145 can reduce OA-induced chondrocyte apoptosis through targeted inhibition on BNIP3 and regulation on Notch signaling pathway.

MiR-155 affects renal carcinoma cell proliferation, invasion and apoptosis through regulating GSK-3β/β-catenin signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 affects renal carcinoma cell proliferation, invasion and apoptosis through regulating GSK-3β/β-catenin signaling pathway, by R.-J. Wei, C.-H. Zhang, W.-Z. Yang, published in Eur Rev Med Pharmacol Sci 2017; 21(22): 5034-5041-DOI: 10.26355/eurrev_201711_13813-PMID: 29228417" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13813.

MiR-203 regulates proliferation and apoptosis of ovarian cancer cells by targeting SOCS3.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-203 regulates proliferation and apoptosis of ovarian cancer cells by targeting SOCS3, by H.-P. Liu, Y. Zhang, Z.-T. Liu, H. Qi, X.-M. Zheng, L.-H. Qi, J.-Y. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9286-9294-DOI: 10.26355/eurrev_201911_19421-PMID: 31773696" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19421.

The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance, by C.-Q. Liang, Y.-M. Fu, Z.-Y. Liu, B.-R. Xing, Y. Jin, J.-L. Huang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21): 5008-5016-PMID: 29164556" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13747.

Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Targeting of GSK-3β by miR-214 to facilitate gastric cancer cell proliferation and decrease of cell apoptosis, by H.-L. Li, S. Liang, J.-H. Cui, G.-Y. Han, published in Eur Rev Med Pharmacol Sci 2018; 22 (1): 127-134-DOI: 10.26355/eurrev_201801_14109-PMID: 29364479" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14109.

Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis, by H. Liu, J.-K. Chang, J.-Q. Hou, Z.-H. Zhao, L.-D. Zhang, published in Eur Rev Med Pharmacol Sci 2017; 21 (14): 3193-3199-PMID: 28770966" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13140.

MiR-155 regulates lymphoma cell proliferation and apoptosis through targeting SOCS3/JAK-STAT3 signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-155 regulates lymphoma cell proliferation and apoptosis through targeting SOCS3/JAK-STAT3 signaling pathway, by X.-D. Li, X.-M. Li, J.-W. Gu, X.-C. Sun, published in Eur Rev Med Pharmacol Sci 2017; 21 (22): 5153-5159-DOI: 10.26355/eurrev_201711_13832-PMID: 29228427" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13832.