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MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.

ABSTRACT: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in carcinogenesis and tumor progression. Previous studies have revealed that MicroRNA-140-5p (miR-140-5p) was abnormally expressed in several cancers. However, its function and possible mechanism in cervical cancer (CC) remains unknown. In this study, the data mining results showed that miR-140-5p was down-regulated in CC specimens and the down-regulation of miR-140-5p was associated with CC poor prognosis. These observations prompted us to further investigate the roles and mechanisms of miR-140-5p in human CC pathogenesis. We found that the over-expression/inhibition of miR-140-5p significantly decreased/increased cell proliferation, migration, and invasion in CC cells in vitro. Meanwhile, the results from in vivo assays showed that the over-expression of miR-140-5p induced significantly suppression of tumor growth and metastasis in nude mice. Furthermore, Insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) was identified as a direct target of miR-140-5p, and both gain-of-function and loss-of-function assays revealed that IGF2BP1 is also a functional target of miR-140-5p. Taken together, our findings suggested a novel miR-140-5p-IGF2BP1 regulatory circuit for CC pathogenesis, and miR-140-5p may be a potential target for CC therapy.

SUBMITTER: Su Y

PROVIDER: S-EPMC5356564 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.

Su Yanlin Y Xiong Jie J Hu Jinyue J Wei Xin X Zhang Xuelian X Rao Lijuan L

Oncotarget 20161001 42

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that play important roles in carcinogenesis and tumor progression. Previous studies have revealed that MicroRNA-140-5p (miR-140-5p) was abnormally expressed in several cancers. However, its function and possible mechanism in cervical cancer (CC) remains unknown. In this study, the data mining results showed that miR-140-5p was down-regulated in CC specimens and the down-regulation of miR-140-5p was associated with CC poor prognosis ...[more]

PMID: 27588393

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Project description:Cervical cancer (CC), also known as invasive cervical carcinoma, is one of the most common gynecologic malignancies. The aim of the present study was to investigate the function of microRNA (miR)-125a-5p on CC progression and cisplatin (DDP) resistance. For this purpose, reverse transcription-quantitative PCR (RT-qPCR) was used to assess the expression of miR-125a-5p and LIMK1 in CC tissues, corresponding normal tissues and cells (human CC cell lines: C-33A, CaSKi; human cervical epithelial cells: HUCEC). Cisplatin (DDP) resistant cervical cancer cell lines were established (C-33A/DDP and CaSKi/DDP cell lines). RT-qPCR results demonstrated that miR-125a-5p or LIM kinase 1 (LIMK1) expression was downregulated or upregulated in C-33A/DDP and CaSKi/DDP cells, respectively. MTT assay, flow cytometry analysis and Western blotting were employed to detect the proliferation, apoptosis rate, IC50 of DDP and the expression of drug resistance-related proteins (P-glycoprotein and glutathione S-transferase-π). The targeting relationship between miR-125a-5p and LIMK1 was confirmed by the TargetScan database and dual-luciferase reporter gene assay. In CC tissues and cell lines, compared with normal tissues or HUCEC, miR-125a-5p expression was downregulated and LIMK1 expression was upregulated. The transfection with miR-125a-5p mimics decreased the proliferation of CaSKi/DDP cells, increased the apoptosis rate, reduced the IC50 of DDP, and downregulated the expression of drug resistance-related proteins; conversely, LIMK1 overexpression decreased the apoptosis rate, increased the IC50 of DDP, and upregulated the expression of drug resistance-related proteins. The luciferase reporter gene assay demonstrated that miR-125a-5p targeted and negatively regulated LIMK1. miR-125a-5p could partially reverse the effect of LIMK1 on the proliferation, apoptosis, IC50 of DDP and the expressions of drug resistance-related proteins. The findings of the present study indicated that miR-125a-5p sensitizes CC cells to DDP by targeting LIMK1, hence increasing the anticancer efficacy of cisplatin.

Dataset Information

MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.

Publications

MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis.

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