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MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma.

ABSTRACT: Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR-876-5p level had a significant shorter overall survival compared to miR-876-5p high-expressing patients. In addition, gain- and loss-of-function experiments demonstrated that miR-876-5p restoration suppressed whereas miR-876-5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR-876-5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR-876-5p reduced c-Met abundance in OS cells and inversely correlated c-Met expression in OS tissues. Herein, c-Met was recognized as a direct target of miR-876-5p using luciferase reporter assay. Notably, c-Met restoration rescued miR-876-5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR-876-5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.

SUBMITTER: Xie W

PROVIDER: S-EPMC6484334 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma.

Xie Weixin W Xiao Jie J Wang Tao T Zhang Dongmei D Li Zhanchun Z

Journal of cellular and molecular medicine 20190217 5

Recently, aberrant expression of miR-876-5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR-876-5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR-876-5p was significantly down-regulated in OS tissues compared to para-cancerous tissues. Clinical association analysis indicated that underexpression of miR-876-5p was positively correlated with advanced clinical stage and poor differentiation. ...[more]

PMID: 30773847

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Project description:BackgroundStudies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174.MethodsHigh-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1).ResultsCompared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value < 0.05). Knockdown of circ_0001174 inhibited the proliferation, migration, and invasion of OS cells. Additionally, circ_0001174 directly and negatively modulated the expression of miR-186-5p and positively regulated the expression of MACC1.ConclusionsAbnormally high expression of circ_0001174 may promote the proliferation, migration, and invasion of OS cells through up-regulating MACC1 by sponging miR-186-5p. These results provide insight into therapeutic targets for preventing and treating OS.

Dataset Information

MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma.

Publications

MicroRNA-876-5p inhibits cell proliferation, migration and invasion by targeting c-Met in osteosarcoma.

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