MicroRNA-139-5p Suppresses Cell Malignant Behaviors in Breast Cancer through Targeting MEX3A
Ontology highlight
ABSTRACT: Objective
The study was designed to evaluate the underlying mechanism of microRNA-139-5p in breast cancer (BC). Methods
Expression statuses of microRNA-139-5p and MEX3A were measured by qRT-PCR and western blotting. The anticancer effect of microRNA-139-5p in vitro was tested by a set of assays. Interaction between microRNA-139-5p and MEX3A was validated by dual-luciferase detection. Results
MicroRNA-139-5p expression in BC cells was obviously low, while MEX3A was significantly overexpressed. MicroRNA-139-5p restrained proliferative, invasive, and migratory abilities of BC cells and increased apoptosis level of BC cells, while MEX3A exerted a promoting effect on BC cell growth. Dual-luciferase reporter detection confirmed that microRNA-139-5p bound to MEX3A 3′-UTR. Conclusions
MicroRNA-139-5p inhibited the development of BC by targeting MEX3A. MicroRNA-139-5p/MEX3A may be a target for BC therapy.
SUBMITTER: Chu J
PROVIDER: S-EPMC8577887 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundMounting evidence has shown circular RNAs (circRNAs) play an important role in the initiation and progression of pancreatic cancer (PC). Meanwhile, circRNAs may serve as the biomarkers for the diagnosis, treatment, and prognosis of PC. Therefore, it is urgent to elucidate the function and underlying mechanism of circRNAs in the development of PC.MethodsThe Cancer-Specific CircRNA Database (CSCD), Circular RNA Interactome database (circinteractome database), and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to verify the expression level of circRNF13 in PC cell lines. Fluorescence in situ hybridization (FISH) and RNase protection assay were used to detect the localization and structure of circRNF13. Then, cell functional experiments were employed to estimate the proliferated, migrated, and invasive abilities in PC. Furthermore, bioinformatic tools, luciferase dual reporter assay, and RT-qPCR were used to investigate the interaction among circRNF13, miR-139-5p, and IGF1R. Eventually, the rescue functional experiments were employed to confirm that circRNF13 targeted the miR-139-5p/IGF1R axis to participate in the development of PC.ResultsCircRNF13 was overexpressed in PC cell lines compared with the normal pancreatic duct cell line. Additionally, inhibition of circRNF13 impaired the proliferation, migration, and invasion of PC cells. CircRNF13 could serve as the molecular sponge of miR-139-5p to inhibit its association with IGF1R that eventually accelerated the malignant progression of PC.ConclusionCircRNF13 serves as a competitive endogenous RNA of IGF1R to inhibit the function of miR-139-5p that eventually reinforces the malignant phenotype of PC.
| S-EPMC8664507 | biostudies-literature
Project description:BackgroundmiR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC).MethodsThe biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling pathway was identified by luciferase activity assay and western blot.ResultsmiR-139-5p was significantly down-regulated in primary tumor tissues (P < 0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay (P < 0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P < 0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1. Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9. Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002).ConclusionsmiR-139-5p plays a pivotal role in colon cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by targeting oncogenic NOTCH1.
| S-EPMC4065091 | biostudies-literature
Project description:Dysfunction of endothelial cells (ECs) and their progenitor cells is an important feature of diabetic vascular disease. MicroRNA (miR)-139-5p is involved in inhibiting the metastasis and progression of diverse malignancies. However, the role of miR-139-5p in ECs still remains unclarified. Here we demonstrated that miR-139-5p expression was elevated in endothelial colony-forming cells (ECFCs) isolated from patients with diabetes, ECs derived from the aorta of diabetic rodents, and human umbilical vein endothelial cells (HUVECs) cultured in high glucose media. MiR-139-5p mimics inhibited tube formation, migration, proliferation, and down-regulated expression of c-jun, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF)-B, in ECFCs and HUVECs, respectively; moreover, miR-139-5p inhibitors reversed the tendency. Further, gain- and-loss function experiments and ChIP assay indicated that miR-139-5p regulate functions of ECFCs by targeting c-jun-VEGF/PDGF-B pathway. In vivo experiments (Matrigel plug assay and hindlimb ischemia model) showed that miR-139-5p downregulation further promoted ECFC-mediated angiogenesis and blood perfusion. In conclusion, diabetes-mediated high miR-139-5p expression inhibits the c-jun-VEGF/PDGF-B pathway, thus decreasing ECFCs migration, tube formation and proliferation, which subsequently reduces ECs survival. Therefore, miR-139-5p might be an important therapeutic target in the treatment of diabetic vasculopathy in the future.
| S-EPMC7835005 | biostudies-literature
Project description:MicroRNAs (miRNAs) have been proven to be involved in cell metastasis and angiogenesis by interaction with the target mRNAs. Evidence has been confirmed that miR-140-5p is a tumor suppressor in human cancers such as breast cancer. However, the potential molecular mechanism of miR-140-5p in breast cancer invasion and angiogenesis is still poorly understood. According to our study, we reported that miR-140-5p inhibited the tumor invasion and angiogenesis of breast cancer cells both in vitro and in vivo by targeting VEGF-A. The mRNA amount of miR-140-5p was decreased in the breast cancer clinical samples and breast cancer with metastasis compared with the corresponding adjacent normal tissues and cancer without metastasis. MiR-140-5p mimics and a negative control were transfected into human MCF-7 and MDA-MB-231 cells. Transwell chambers were used to detect the invasive ability of the cells, and the angiogenic ability was assessed by tube-formation assay. The markers of invasion and angiogenesis, VEGF-A, CD31 and MMP-9, were detected by using immunohistochemistry and western blot analysis in vivo. VEGF-A was verified as a possible target gene of miR-140-5p, and corroborated by dual-luciferase reporter and ELISA. Taken together, the study elucidates the molecular mechanisms by which miR-140-5p inhibits breast cancer metastasis and angiogenesis, and provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for breast cancer patients.
| S-EPMC5668497 | biostudies-literature
Project description:G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand-receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development.
| S-EPMC4832062 | biostudies-literature
Project description:BackgroundAstrocytoma is a common tumor type in primary central nervous system and has a high death rate around the world. Aberrant expression of long non-coding RNAs (lncRNAs) has been introduced by emerging studies to result in the development of diverse cancers.MethodsRT-qPCR examined the expression of SNHG17, miR-876-5p and ERLIN2, and western blot evaluated ERLIN2 protein level. RNA pull down and luciferase reporter assays illustrated the relationships between SNHG17 and its downstream molecules.ResultsSNHG17 was up-regulated in astrocytoma cells. Moreover, SNHG17 silence could repress the proliferation, migration and invasion of astrocytoma cells. Besides, miR-876-5p was selected out as a downstream molecule of SNHG17 in astrocytoma. ERLIN2 was determined to be targeted by miR-876-5p. ERLIN2 mRNA and protein levels were lessened by miR-876-5p overexpression and SNHG17 silence. Additionally, miR-876-5p overexpression decelerated the biological processes of astrocytoma cells, so did ERLIN2 knockdown. More importantly, the impacts of SNHG17 down-regulation on the malignant behaviors of astrocytoma cells were counteracted by overexpressed ERLIN2 or inhibited miR-876-5p.ConclusionsSNHG17 could induce the progression of astrocytoma by sponging miR-876-5p to elevate the expression of ERLIN2. This study indicated that SNHG17 has a high potential to be a therapeutic target for astrocytoma.
| S-EPMC7469335 | biostudies-literature
Project description:BackgroundmiR-196b-5p expression is deregulated in many malignant tumors. Although miR-196b-5p has been implicated in the malignant transformation of colorectal cancer, its role in this specific type of cancer has not been fully explored. Thus, the present study was aimed to examine the cellular function of miR-196b-5p and its role in malignant biological behavior in colorectal cancer.MethodsmiR-196b-5p expression was measured in colorectal cancer tissues and cell lines using quantitative real-time PCR. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect proliferation, migration, and invasion in cell lines, whereas flow cytometry was applied to study apoptosis. Western blot analysis was performed to measure the protein levels. Dual luciferase reporter assay was used to investigate the interaction between miR-196b-5p and ING5. Tumor formation was evaluated in mice.ResultsMiR-196b-5p was abundantly expressed in colorectal cancer tissues and cell lines, whereas ING5 was expressed at low levels. MiR-196b-5p was successfully overexpressed or knocked down in colorectal cancer cells. We found that miR-196b-5p overexpression significantly accelerated the proliferation, cell cycle, migration and invasion, while inhibited cell apoptosis in colorectal cancer cells. However, miR-196b-5p inhibitor showed the opposite effects. Moreover, ING5 overexpression or knockdown was successfully performed in colorectal cancer cells. ING5 overexpression suppressed proliferation, migration, invasion, the phosphorylation of PI3K, Akt as well as MEK, and promoted cell apoptosis, which could be reversed by ING5 knockdown. Additionally, ING5 was identified as a target of miR-196b-5p through bioinformatics analysis and a luciferase activity assay. Furthermore, ING5 knockdown could attenuate the decrease in proliferation, migration, invasion, and the protein levels of p-PI3K, p-Akt, and p-MEK, which were induced by miRNA-196b-5p inhibitor. Besides, miR-196b-5p knockdown inhibited tumor growth, whereas ING5 knockdown elevated it in vivo.ConclusionsIn conclusion, miR-196b-5p promotes cell proliferation, migration, invasion, and inhibits apoptosis in colorectal cancer by targeting ING5.
| S-EPMC7149860 | biostudies-literature
Project description:To provide better therapeutic avenues for treating tongue squamous cell carcinoma (TSCC), a series of experiments about the effects of microRNA (miR)-532-3p on TSCC malignant behaviors were carried out. The result showed that miR-532-3p was down-regulated and C-C chemokine receptor 7 (CCR7) was up-regulated in the tumor tissues compared with those in the paired paratumor tissues. Further, expression of miR-532-3p was detected in four TSCC cell lines, TSCCA, TCA8113, CAL-27, and SCC-25. The miR-532-3p mimics and inhibitor were transfected into the CAL-27 and TCA8113 cell lines which were the relatively lowest and highest miR-532-3p expressions, respectively. It was found that the overexpression of miR-532-3p suppressed TSCC cell proliferation, migration, invasion, and promoted apoptosis in vitro, whilst the knockdown of miR-532-3p reversed these behaviors. The bioinformatics predicted that CCR7 was a downstream gene of miR-532-3p, which was confirmed via luciferase assay. Following, the decline of CCR7 in the miR-532-3p mimics group and the rise of CCR7 in the miR-532-3p inhibitor group were also verified. In addition, enhanced cell proliferation, migration and invasion induced by CCR7 were partly restrained by miR-532-3p in TSCC cell. Meanwhile, miR-532-3p attenuated tumourigenesis in vivo due to the reduction of tumor volume and Ki-67 positive rate and the increase of apoptotic cells. Taken together, these findings reveal a pivotal role for the miR-532-3p/CCR7 axis in regulating TSCC, and this novel axis could be suitable for therapeutic intervention in TSCC disease.
| S-EPMC6727182 | biostudies-literature
Project description:BackgroundIn recent years, gene expression-based analysis has been used for disease biomarker discovery, providing ways for better diagnosis, leading to improvement of clinical treatment efficacy. This study aimed to explore the role of miR-16-5p and ANLN in breast cancer (BC).MethodsCohort datasets of BC were obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) and analyzed by bioinformatics tools. qRT-PCR and western blotting were applied to validate ANLN and its protein expression. A dual-luciferase reporter assay was used to prove the regulatory relationship of miR-16-5p and ANLN. Finally, MTT, wound healing, Transwell invasion and flow cytometry analyses of the cell cycle and apoptosis were performed to assess cell proliferation, migration, invasion, cell cycle and apoptosis, respectively.ResultsA total of 195 differentially expressed genes (DEGs) and 50 overlapping microRNAs (miRNAs) were identified. Among these DEGs and miRNAs, ANLN, associated with poor overall survival in BC, overlapped in the GSE29431, GSE42568, TCGA and GEPIA2 databases. Moreover, ANLN was highly expressed, while miR-16-5p was lower in BC cells than in breast epithelial cells. Then, we confirmed that ANLN was directly targeted by miR-16-5p in BC cells. Over-expression of miR-16-5p and knock-down of ANLN remarkably inhibited cell proliferation and migration as well as cell invasion, arrested the cells in G2/M phase and induced apoptosis in BC cells.ConclusionsThese findings suggest that miR-16-5p restrains proliferation, migration and invasion while affecting cell cycle and promotes apoptosis by regulating ANLN, thereby providing novel candidate biomarkers for the diagnosis and treatment of BC.
| S-EPMC8574041 | biostudies-literature
Project description:Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.
| S-EPMC7076186 | biostudies-literature