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MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

ABSTRACT: MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in carcinogenesis. In this study, we investigated the biological function and mechanism of miR-613 in the regulation of papillary thyroid cancer (PTC) development. We found that miR-613 was downregulated in PTC cell lines and tissues, and overexpression of miR-613 significantly suppressed PTC cell growth, migration and invasion in vitro and inhibited tumor growth in vivo. We identified the gene for sphingosine kinase 2 (SphK2) as a direct target of miR-613. Overexpression of miR-613 significantly repressed SphK2 expression by directly targeting its 3'-untranslated regions (3'-UTR) and restoration of SphK2 reversed the inhibitory effects of miR-613 on PTC cell growth and invasion. Taken together, our results indicated that miR-613 functions as a tumor suppressor in PTC and its suppressive effect is mediated by repressing SphK2 expression.

SUBMITTER: Qiu W

PROVIDER: S-EPMC5129980 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

Qiu Wangwang W Yang Zhili Z Fan Youben Y Zheng Qi Q

Oncotarget 20160601 26

MicroRNAs (miRNAs) have emerged as important gene regulators and are recognized as key players in carcinogenesis. In this study, we investigated the biological function and mechanism of miR-613 in the regulation of papillary thyroid cancer (PTC) development. We found that miR-613 was downregulated in PTC cell lines and tissues, and overexpression of miR-613 significantly suppressed PTC cell growth, migration and invasion in vitro and inhibited tumor growth in vivo. We identified the gene for sph ...[more]

PMID: 27223438

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Project description:IntroductionMicroRNAs (miRNAs) are small noncoding RNA molecules that regulate genetic expression and are also vital for tumor initiation and development. MiR-29b-3p was found to be involved in regulating various biological processes of tumors, including tumor cell proliferation, metastasis, and apoptosis inhibition; however, the biofunction and molecule-level mechanisms of miR-29b-3p inpapillary thyroid carcinoma (PTC) remain unclear.MethodsThe expression of miR-29b-3p in PTC samples was tested via qRT-PCR. Cellular proliferation was analyzed by CCK-8 and EdU assays, and cellular migratory and invasive abilities were assessed utilizing wound-healing and Transwell assays. In addition, protein expressions of COL1A1, COL5A1, E-cadherin, N-cadherin, Snail, and Vimentin were identified via Western blot (WB) assay. Bioinformatics, qRT-PCR, WB, and dual luciferase reporter assays were completed to identify whether miR-29b-3p targeted COL1A1 and COL5A1. In addition, our team explored the treatment effects of miR-29b-3p on a murine heterograft model.ResultsOur findings revealed that miR-29b-3p proved much more regulated downward in PTC tissue specimens than in adjacent non-cancerous tissues. Meanwhile, decreased expression of miR-29b-3p was strongly related to the TNM stage of PTC patients (p<0.001), while overexpression of miR-29b-3p in PTC cells suppressed cellular migration, invasion, proliferation, and EMT. Conversely, silencing miR-29b-3p yielded the opposite effect. COL1A1 and COL5A1 were affirmed as the target of miR-29b-3p. Additionally, the COL1A1 and COL5A1 were highly expressed in PTC tumor samples than in contrast to neighboring healthy samples. Functional assays revealed that overexpression of COL1A1 or COL5A1 reversed the suppressive role of miR-29b-3p in migration, invasion, and EMT of PTC cells. Finally, miR-29b-3p agomir treatment dramatically inhibited Xenograft tumor growth in the animal model.ConclusionsThese findings document that miR-29b-3p inhibited PTC cells invasion and metastasis by targeting COL1A1 and COL5A1; this study also sparks new ideas for risk assessment and miRNA replacement therapy in PTC.

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MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

Publications

MicroRNA-613 inhibits cell growth, migration and invasion of papillary thyroid carcinoma by regulating SphK2.

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