MiR-34a-5p might have an important role for inducing apoptosis by down-regulation of SNAI1 in apigenin-treated lung cancer cells.
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ABSTRACT:
SUBMITTER: Aida R
PROVIDER: S-EPMC8060201 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MiR-34a-5p has been implicated in the tumorigenesis and progression of several types of cancer. However, the role of miR-34a-5p in osteosarcoma (OS) remains largely unknown. This study was performed in two multi-chemosensitive (G-292 and MG63.2) and two resistant (SJSA-1 and MNNG/HOS) OS cell lines. MiR-34a-5p promotes OS multi-chemoresistance via its repression of the Delta-like ligand 1 (DLL1) gene, the ligand of the Notch pathway, and thus negatively correlates with OS chemoresistance. The siRNA-mediated repression of the DLL1 gene suppressed cell apoptosis and de-sensitized G-292 and MG63.2 cells, while overexpression of DLL1 sensitized SJSA-1 and MNNG/HOS cells to drug-induced cell death. In agreement with the changes in the drug-induced cell death, the activity of the ATF2/ATF3/ATF4 signaling pathway was significantly altered by a forced reversal of miR-34a-5p or DLL1 levels in OS cells. DLL1 is a target of miR-34a-5p and negatively regulates the multi-chemoresistance of OS. This study suggested that miR-34a-5p, DLL1 and the ATF2/ATF3/ATF4 signaling pathway-associated genes are the potential diagnostic and/or therapeutic targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients.
| S-EPMC5345075 | biostudies-literature
Project description:MicroRNA 34a (miR-34a) is a tumor suppressor gene, but how it regulates cell proliferation is not completely understood. We now show that the microRNA miR-34a regulates silent information regulator 1 (SIRT1) expression. MiR-34a inhibits SIRT1 expression through a miR-34a-binding site within the 3' UTR of SIRT1. MiR-34 inhibition of SIRT1 leads to an increase in acetylated p53 and expression of p21 and PUMA, transcriptional targets of p53 that regulate the cell cycle and apoptosis, respectively. Furthermore, miR-34 suppression of SIRT1 ultimately leads to apoptosis in WT human colon cancer cells but not in human colon cancer cells lacking p53. Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway.
| S-EPMC2533205 | biostudies-literature
Project description:BACKGROUND:Osteoarthritis (OA) is one of the most common rheumatic diseases of which clinical symptoms includes swelling, synovitis and inflammatory pain, affect patients' daily life. It was reported that non-coding RNAs play vital roles in OA. However, the regulation mechanism of ncRNA in OA pathogenesis has not been fully elucidated. METHODS:The expression of SNHG7, miR-34a-5p and SYVN1 was detected using qRT-PCR in tissues, serum and cells. The protein expression of SYVN1, PCNA, cleavage-caspase 3, beclin1 and LC3 were measured using western blot. The RNA immunoprecipitation (RIP), RNA pulldown, and luciferase reporter assays were used to verify the relationship between SNHG7, miR-34a-5p and SYVN1. The MTT and flow cytometry assay was performed to detected cell proliferation and cell apoptosis respectively. RESULTS:In this study, SNHG7 and SYVN1 expression were down-regulated, but miR-34a-5p was up-regulated in OA tissues and IL-1β treated cells compared with normal tissues and chondrocyte. Functional investigation revealed that up-regulated SNHG7 or down-regulated miR-34a-5p could promote cell proliferation and inhibit cell apoptosis and autophagy in OA cells. More than that, RIP, pulldown and luciferase reporter assay was applied to determine that miR-34a-5p was a target miRNA of SNHG7 and SYVN1 was a target mRNA of miR-34-5p. Rescue experiments showed that overexpression of miR-34a reversed high expression of SNHG7-mediated suppression of apoptosis and autophagy as well as promotion of proliferation, while its knockdown inhibited cell apoptosis and autophagy and promoted cell proliferation which could be impaired by silencing SYVN1. In addition, SNHG7 regulated SYVN1 through sponging miR-34a-5p. CONCLUSION:SNHG7 sponged miR-34a-5p to affect cell proliferation, apoptosis and autophagy through targeting SYVN1 which provides a novel sight into the pathogenesis of OA.
| S-EPMC7027214 | biostudies-literature
Project description:Objective: The pancreatic endocrinal system dominates the regulation of blood glucose levels in vivo, and the dysfunction of pancreatic endocrine β-cells is a major cause of the occurrence and development of Type 2 diabetes (T2D). Although microRNA (miRNA) have been found to be key regulators of pancreatic β-cells proliferation, differentiation and apoptosis, the underlying mechanism remains enigmatic. The aim of this study was to identify several novel miRNAs which might be involved in the etiopathogenesis of diabetic β-cells dysfunction. Methods: The miRNA expression profiles in the pancreas of high-fat diet (HFD) fed Zucker diabetic fatty (ZDF) rats and Zucker lean (ZL) rats feed with normal-fat diet (NFD) were detected by using miRNA microarray chip, and individually verified the most significant factors by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to predict the target genes related to each of the identified miRNAs and the functions of these target genes in different metabolic signaling pathways. Results: Compared with the ZL rats, a total of 24 differentially expressed miRNAs were detected in ZDF rats. Among which miR-34a-5p and miR-452-5p were the most significantly up-regulated and down-regulated respectively. These miRNAs have not been reported in rats' pancreas before. By GO and KEGG enrichment analyses, we found that miR-34a-5p could negatively regulate pancreatic β-cell proliferation through the involvement of Wnt signaling pathway. In addition, it was also found to regulate insulin secretion through the insulin signaling pathway to modulate blood glucose levels. At the same time, miR-452-5p was found to positively regulate the activity of the key rate-limiting enzyme branched-chain α-keto acid dehydrogenase-β (BCKDHB) in the catabolism of branched chain amino acids (BCAA), leading to mitochondrial dysfunction in pancreatic β-cells. Conclusions: miR-34a-5p and miR-452-5p were identified as the novel regulators of pancreatic endocrine dysfunction. These miRNAs might have the potential to be utilized as the new predictive biomarkers for the diagnosis of the occurrence and development of T2D, as well as the therapeutic targets for T2D treatment.
| S-EPMC8364455 | biostudies-literature
Project description:BackgroundNeonatal sepsis is a serious condition. Recent clinical studies have indicated that microRNAs (miRNAs) are key players in the pathogenesis of sepsis, which could be used as biomarkers for this condition.Patients and methodsA total of 90 neonates with sepsis and 90 healthy neonates were enrolled in this study. qRT-PCR was performed to measure the expression levels of serum miR-34a-5p and miR-199a-3p.ResultsmiR-34a-5p and miR-199a-3p serum levels were significantly reduced in neonates with sepsis compared with those in healthy neonates (P = 0.006 and P = 0.001, respectively). Significant correlations of miR-34a-5p and miR-199a-3p with each of TLC, RDW, RBS, and C-reactive protein (CRP) as well as SNAPII were observed, indicating their associations with the severity of neonatal sepsis.ConclusionmiR-34a-5p and miR-199a-3p may be useful as novel biomarkers in neonatal sepsis and may provide a new direction for its treatment.
| S-EPMC8735601 | biostudies-literature
Project description:BackgroundAlthough a pivotal role of microRNA (miRNA, miR) in the pathogenesis of Huntington's disease (HD) is increasingly recognized, the molecular functions of miRNAs in the pathomechanisms of HD await further elucidation. One of the miRNAs that have been associated with HD is miR-34a-5p, which was deregulated in the mouse R6/2 model and in human HD brain tissues.MethodsThe aim of our study was to demonstrate interactions between miR-34a-5p and HD associated genes. By computational means we predicted 12 801 potential target genes of miR-34a-5p. An in-silico pathway analysis revealed 22 potential miR-34a-5p target genes in the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway "Huntington's disease".ResultsUsing our high-throughput miRNA interaction reporter assay (HiTmIR) we identified NDUFA9, TAF4B, NRF1, POLR2J2, DNALI1, HIP1, TGM2 and POLR2G as direct miR-34a-5p target genes. Direct binding of miR-34a-5p to target sites in the 3'UTRs of TAF4B, NDUFA9, HIP1 and NRF1 was verified by a mutagenesis HiTmIR assay and by determining endogenous protein levels for HIP1 and NDUFA9. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) analysis identified protein-protein interaction networks associated with HD like "Glutamine Receptor Signaling Pathway" and "Calcium Ion Transmembrane Import Into Cytosol".ConclusionOur study demonstrates multiple interactions between miR-34a-5p and HD associated target genes and thereby lays the ground for future therapeutic interventions using this miRNA.
| S-EPMC10295337 | biostudies-literature
Project description:Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.
| S-EPMC4741860 | biostudies-literature
Project description:Radioresistance is a challenge in the treatment of esophageal squamous cell carcinoma (ESCC). MicroRNAs (miRNAs) are known to play an important role in the functional modification of cancer cells and recent studies have reported miRNA-mediated radiotherapy resistance. However, further research is necessary to reveal the regulation mechanisms, and treatment strategies using miRNA are yet to be established for ESCC. We compared the miRNA expression profiles of ESCC parental (TE-4) and acquired radioresistance (TE-4R) cell lines using a miRNA microarray and qRT-PCR. Our data showed that miR-338-5p, one of the target miRNA biomarkers, was significantly downregulated in TE-4R. Ectopic overexpression of miR-338-5p induced apoptosis and sensitivity to radiation treatment by interfering with survivin, which is a known inhibitor of apoptosis. Overexpression of survivin reversed miR-338-5p-induced apoptosis. Tumor xenograft experiments indicated that therapeutic delivery of the miR-338-5p mimics via direct injection into tumor mass increased sensitivity to radiation therapy. In conclusion, our findings suggest that miR-338-5p is a potential radiosensitizer and may be a therapeutic biomarker for radioresistant in ESCC.
| S-EPMC5589838 | biostudies-literature
Project description:The specific causes of recurrent spontaneous abortion (RSA) remain unknown in 37-79% of affected women. The aim of this study was to explore the expression levels of 6 miRNAs in natural killer (NK) cells from the decidua of patients with unexplained RSA (URSA) and to predict the target genes of 3 miRNAs.Two groups were examined: URSA (n=20) and controls (n=20). Flow cytometry analysis was used to identify NK cells isolated from the decidua. Transcriptional levels of miRNA were monitored using quantitative real-time reverse transcription-polymerase chain reaction. Prediction and analysis of mRNA targets of differentially expressed miRNAs were performed using bioinformatics methods.Five miRNAs [miR-34a (+281%, P<0.001), miR-155 (+396%, P<0.001), miR-141 (+142%, P<0.01), miR-125a (+279%, P<0.001), and miR-125b (+185%, P<0.001)] were up-regulated, while miR-24 was down-regulated (-64%, P<0.01) in the URSA group, compared to the control group. This study identified potential miRNA targets: miR-34a-3p/5p, 585/1718 (targets of miR-34a-3p/targets of miR-34a-5p), miR-141-3p/5p, 2270/629 (targets of miR-141-3p/targets of miR-141-5p), and miR-24, 2320 target genes. A total of 140 pathways related to target genes were identified including PI3K-Akt, focal adhesion, MAPK, Wnt, regulation of the actin cytoskeleton, T cell receptor, TGF-?, and estrogen signaling pathways.This study suggests that miR-34a-3p/5p, miR-141-3p/5p, and miR-24 in decidual NK cells could be associated with URSA. These findings might contribute to the panel of diagnostic and prognostic biomarkers with clinical utility, and facilitate the development of new strategies for targeted therapy against URSA.
| S-EPMC4805134 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a group of noncoding RNAs derived from back-splicing events. CircRNA is reported to be involved in various tumor progressions, including glioma. Although there are a few reports of circular RNAs participating in gliomas, it is still unclear whether circular RNAs regulate the occurrence of gliomas. In our research, we found that the expression of circITGA7 in glioma tissues and glioma cells increased significantly. Knocking down circITGA7 can significantly inhibit the proliferation of glioma cells and reduce cell metastasis. Through analysis and dual-luciferase report assay, we found that circITGA7 acts as a sponge for miR-34a-5p targeting VEGFA in glioma. Our study showed that circITGA7 regulates the proliferation and metastasis of glioma cell lines (SW1783&U373) by regulating the miR-34a-5p/VEGFA pathway. In conclusion, our study revealed a regulatory loop for the circITGA7/miR-34a-5p/VEGFA axis to regulate glioma development.
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