MiR-342-3p Regulates the Proliferation and Apoptosis of NSCLC Cells by Targeting BCL-2.
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ABSTRACT:
SUBMITTER: Chen Z
PROVIDER: S-EPMC8445541 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fast growth and hardly any apoptosis are important characteristics of breast cancer, which assure the spread via invasion and metastasis of breast cancer cells. Inhibition of fast proliferation and induction of apoptosis are critical way to cure this cancer. microRNAs (miRNAs) had been increasingly reported to be the critical regulator of tumorigenesis. In our study, we found that increasing copy number of miR-548d-2-3p is critically involved poor prognosis. We overexpressed miR-548d-3p in MDA-MB-231cells and found that the proliferation was promoted significantly, whereas the inhibition of miR-548d-3p repressed the proliferation of MDA-MB-231 cells and also induced the increase in apoptosis. Additionally, we found that miR-548d-3p downregulated the expression of TP53BP2 by directly targeting the 3'UTR. We also found that knockdown of TP53BP2 significantly resorted the proliferation and apoptosis regulated by miR-548d-3p inhibitor. Our study showed that miR-548d-3p/TP53BP2 pathway is critically involved in the proliferation and apoptosis of breast cancer cells and may be new therapeutic target of breast cancer cells.
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Project description:Accumulating evidence suggests that microRNAs (miRNAs) play a key role in the biological behaviors and progression of glioma. However, the function and bio‑molecular mechanisms of miR‑342 in glioma remain largely unclear. In the present study, reverse transcription quantitative‑polymerase chain reaction and western blotting were performed to determine the mRNA and protein expression levels of the factors investigated. MTT assay was performed to examine the proliferation rates. Luciferase reporter assay was performed to test the binding between miRNA‑342 and its putative target. Data indicated that miR‑342 expression was markedly decreased in human glioma tissues and cell line U87, and reduced miR‑342 expression significantly promoted cell proliferation. In order to explore the mechanisms, G‑protein coupled receptor family C group 5 member A (GPRC5A) was identified as a target of miR‑342 and depletion of GPRC5A suppressed cell proliferation. Our findings demonstrated that miR‑342 regulates the cell proliferation of glioma by targeting GPRC5A, which indicates that miR‑342 is a target of interest regarding the treatment of refractory glioma, and it may provide a promising prognostic and therapeutic strategy for glioma treatment.
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Project description:BackgroundIt is well known that microRNAs (miRNAs) interfere with the progression of various human malignancies. This article is aimed at exploring the regulating role of miR-342-3p in acute myeloid leukemia (AML) and its mechanism.MethodsWe used the Gene Expression Omnibus (GEO) database to determine miR-342-3p differential expression patterns in AML patients' plasma and cells as well as healthy individuals' plasma and T cells. Quantitative real-time PCR and Western blotting were performed for plasma and cell miR-342-3p and SRY-related high-mobility-group box (SOX12) expression quantification, and cell counting kit-8 assay and flow cytometry were used for the determination of AML cell growth, cycle, and apoptosis. A dual-luciferase reporter gene assay was further carried out to identify the targeted association between miR-342-3p and SOX12 mRNA 3'UTR after prediction by a bioinformatics website. Pearson's correlation analysis was performed to analyze the connection between miR-342-3p and SOX12 expressions. The LinkedOmics database was utilized to explore the downstream pathways in which SOX12 was enriched.ResultsEvidently downregulated plasma miR-342-3p and markedly elevated SOX12 were observed in AML patients versus healthy individuals. miR-342-3p mimics suppressed AML cell growth, enhanced apoptosis, and induced G0/G1 phase arrest; conversely, enhanced capacity of AML cells to proliferate, suppressed apoptosis, and accelerated cell cycle were observed after treatment with miR-342-3p inhibitors. SOX12 was confirmed as miR-342-3p's target gene. Overexpressing or knocking down SOX12 reversed miR-342-3p's impacts on AML cell growth, apoptosis, and cycle. Upregulated SOX12 was positively related to DNA replication and RNA polymerase signaling pathways.ConclusionmiR-342-3p affects apoptosis of AML cells and their ability to proliferate via targeted regulation of SOX12.
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Project description:The proliferation and apoptosis of granulosa cells (GCs) affect follicle development and reproductive disorders, with microRNAs playing a crucial regulatory role. Previous studies have shown the differential expression of miR-128-3p at different stages of goat follicle development, which suggests its potential regulatory role in follicle development. In this study, through the Cell Counting Kit-8 assay, the EDU assay, flow cytometry, quantitative real-time polymerase chain reaction, Western blot, and the dual-luciferase reporter assay, we used immortal human ovarian granulosa tumor cell line (KGN) cells as materials to investigate the effects of miR-128-3p and its predicted target gene growth hormone secretagogue receptor (GHSR) on GC proliferation and apoptosis. The results show that overexpression of miR-128-3p inhibited the proliferation of KGN cells, promoted cell apoptosis, and suppressed the expression of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (BCL2) while promoting that of Bcl-2 associated X protein (BAX). The dual-luciferase reporter assay revealed that miR-128-3p bound to the 3' untranslated region sequence of GHSR, which resulted in the inhibited expression of GHSR protein. Investigation of the effects of GHSR on GC proliferation and apoptosis revealed that GHSR overexpression promoted the expression of PCNA and BCL2, enhanced GC proliferation, and inhibited cell apoptosis, whereas the opposite effects were observed when GHSR expression was inhibited. In addition, miR-128-3p and GHSR can influence the expression of extracellular signal-regulated kinase 1/2 protein. In conclusion, miR-128-3p inhibits KGN cell proliferation and promotes cell apoptosis by downregulating the expression of the GHSR gene.
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Project description:BackgroundGlioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma.MethodsBioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342-3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules.ResultsWe first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342-3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival.ConclusionsOur study identified a novel feedback loop among U2AF2, cARF1, miR-342-3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.
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Project description:Lung cancer is the most common incident cancer, with a high mortality worldwide, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of cases. Numerous studies have shown that the aberrant expression of microRNAs (miRNAs) is associated with the development and progression of cancers. However, the clinical significance and biological roles of most miRNAs in NSCLC remain elusive. In this study, we identified a novel miRNA, miR-34b-3p, that suppressed NSCLC cell growth and investigated the underlying mechanism. miR-34b-3p was down-regulated in both NSCLC tumour tissues and lung cancer cell lines (H1299 and A549). The overexpression of miR-34b-3p suppressed lung cancer cell (H1299 and A549) growth, including proliferation inhibition, cell cycle arrest and increased apoptosis. Furthermore, luciferase reporter assays confirmed that miR-34b-3p could bind to the cyclin-dependent kinase 4 (CDK4) mRNA 3'-untranslated region (3'-UTR) to suppress the expression of CDK4 in NSCLC cells. H1299 and A549 cell proliferation inhibition is mediated by cell cycle arrest and apoptosis with CDK4 interference. Moreover, CDK4 overexpression effectively reversed miR-34-3p-repressed NSCLC cell growth. In conclusion, our findings reveal that miR-34b-3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR-34b-3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.
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Project description:Skeletal muscle plays an important role in the growth and development of meat animals. MicroRNAs (miRNAs) can participate in the regulation of muscle development-related functions; however, there have been few reports on whether there are related miRNAs that conservatively regulate muscle development among different species. In this study, the miRNA transcriptome sequencing data of the muscle tissue of cattle, rat, goat, and pig showed that miR-24-3p may conservatively regulate muscle development in these species. Furthermore, mmu-miR-24-3p can positively regulate C2C12 cell proliferation and apoptosis by regulating key proliferation and apoptosis genes in muscle development, which was verified by CCK-8 and RT-qPCR. Bta-miR-24-3p can also positively regulate the proliferation and apoptosis of bovine muscle primary cells by regulating key proliferation and apoptosis genes in the process of muscle development, as verified by CCK-8 and RT-qPCR. The target genes of miR-24-3p in cattle, rat, goat, and pig, which include a large proportion of target genes shared among the four species, are enriched in multiple cell functions and signal pathways that are closely related to muscle development, as revealed by GO and KEGG enrichment analysis. A double luciferase test showed that the shared target genes WNT4, CAMK2B, and TCF7 were targeted by mmu-miR-24-3p in rat and bta-miR-24-3p in cattle. These three shared target genes WNT4, CAMK2B, and TCF7 are involved in the Wnt signaling pathway, which showed that miR-24-3p plays an important role in rat and cattle. The shared target gene (CAMK2B) in rat and cattle increased significantly after the inhibition of miR-24-3p by RT-qPCR. The findings of this study contribute to a better understanding of the role of miR-24-3p in the regulation of muscle development.
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Project description:Background:Aberrant expression of long non-coding RNAs (lncRNAs) is closely associated with development and prognosis of human cancers. LncRNA SNHG16 is reportedly involved in human cancer; however, its roles in multiple myeloma (MM) remain unclear. Methods:In this study, we investigated the function and molecular mechanisms of SNHG16 in MM. MM cells were transfected with si-SNHG16 or si-NC. SNHG16 expression levels was measured by qRT-PCR. Cell proliferation was monitored using the MTS. Flow cytometry assay was performed to measure the cell cycle and apoptosis. Luciferase reporter assay were performed to confirm the sponged miRNAs of SNHG16. Results:SNHG16 expression was up-regulated in MM tissues. SNHG16 knockdown suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted the apoptosis of MM cells. Moreover, SNHG16 knockdown promoted cleaved-Caspase-3, cleaved-Caspase-9, Foxa3a, and Bax expression, while markedly inhibiting CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. miR-342-3p was a direct target of SNHG16. SNHG16 knockdown significantly increased miR-342-3p expression in MM cells. Overexpression miR-342-3p markedly suppressed cell proliferation, arrested cell cycle transition from G1 to S phase, and promoted apoptosis of MM cells. Overexpression of miR-342-3p markedly promoted cleaved-Caspase-3/-9, Foxa3a, and Bax expression, and inhibited CCND1, Bcl-2, Cyclin D1, PI3K, and p-AKT expression in MM cells. Additionally, repression of miR-342-3p could rescue the effect of SNHG16 knockdown on MM cell proliferation, cycle arrest, apoptosis, and related protein expression. Conclusion:Knockdown of lncRNA SNHG16 suppresses MM cell proliferation by sponging miR-342-3p, implicating SNHG16 as a novel therapeutic target for MM.
| S-EPMC6998159 | biostudies-literature
Project description:Purpose: Cancer stem cells (CSCs) initiate and maintain tumorigenesis due to their unique pluripotency. However, pancreatic stem cell gene signatures are not completely revealed yet. Here, we isolated pancreatic cancer stem cells (P-CSCs) and exploited their distinct genome-wide mRNA and miRNA expression profiles using microarrays. Methods: CD24+ CD44+ ESA+ cells were isolated from two pancreatic xenograft cells by the flow cytometry and identified the stem cell-like properties by the tumor formation, self-renew and chemoresistance. Microarrays and qRT-PCR were used to exploit their distinct Genome-wide mRNA and miRNA expression profiles. The function and candidate target genes of key microRNA were detected after Ectopic restoration in the pancreatic cancer cell lines MIA Paca-2 (CSChigh) and BxPC-3 (CSClow). Results: In this study, we isolated P-CSCs from two xenografts cells. Genome-wide profiling experiments showed 479 genes and 15 microRNAs specifically expressed in the P-CSCs, including genes involved in TGF-β and p53 signaling pathways and particularly miR-146b-3p as the most significantly downregulated miRNA. We confirmed miR-146b-3p as a downregulated signature in pancreatic cancer tissues and cell line MIA Paca-2 (CSChigh) cells. Ectopic restoration of miR-146b-3p expression with pre-miR reduced cell proliferation, induced apoptosis, increased G1 phase and reduced S phase in cell cycle in MIA Paca-2 (CSChigh), but not in BxPC-3 (CSClow). Re-expression of miR-146b-3p with lentivirus significantly inhibited tumorigenicity in vivo in MIA Paca-2, but slightly in BxPC-3. Furthermore, we demonstrated that miR-146b-3p directly targeted MAP3K10 and might activate Hedgehog pathway as well through DYRK2 and GLI2. Conclusions: These results suggest that P-CSCs have distinct gene expression profiles. MiR-146b-3p inhibits proliferation and induced apoptosis in P-CSCs high cells lines by targeting MAP3K10. Targeting P-CSCs specific genes may provide novel strategies for therapeutic purposes.
| S-EPMC8120187 | biostudies-literature
Project description:BackgroundThe incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide.ObjectivesAlthough previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma.Materials and methodsReal-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression.ResultsThe expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT).ConclusionmiRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting elF4B gene and then blocked the PI3K-AKT signaling pathway.SignificanceThe role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.
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