MiR-362-3p functions as a tumor suppressor through targeting MCM5 in cervical adenocarcinoma.

Biosci Rep 2018 06 21;38(3). Epub 2018 Jun 21.

Department of Gynecology, Jining No.1 People's Hospital, Jining 272000, Shandong, China

Our previous study suggested that minichromosome maintenance protein 5 (MCM5) overexpression was observed in cervical adenocarcinoma and closely associated with advanced clinical stage, more metastatic lymph nodes, present distant metastasis, low histological grade, and poor prognosis. Down-regulation of MCM5 inhibited cervical adenocarcinoma cell proliferation. The purpose of the present study is to search and confirm valuable microRNAs (miRNAs), which target MCM5 to modulate cervical adenocarcinoma cell proliferation. In our results, we found that levels of miR-362-3p expression were reduced in cervical adenocarcinoma tissues and cell lines. Moreover, 3'-UTR of MCM5 had binding site of miR-362-3p through analyzing Targetscan database and miRanda database, and there were an inverse association between miR-362-3p and MCM5 in cervical adenocarcinoma tissues. Furthermore, we verified miR-362-3p directly targeted to 3'-UTR of DCLK1 by luciferase reporter assay, and negatively regulated mRNA and protein expressions of MCM5 by qPCR and Western blot. Then, we conducted gain-of-function study and rescued-function study, and found that miR-362-3p served as a tumor suppressive miRNA to modulate cervical adenocarcinoma cell proliferation through regulating the functional target MCM5. Finally, we analyzed correlations between miR-362-3p expression and clinicopathological characteristics and observed that miR-362-3p low expression was associated with advanced clinical stage and poor prognosis. In conclusion, miR-362-3p is a tumor suppressive miRNA in cervical adenocarcinoma.

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Source
http://dx.doi.org/10.1042/BSR20180668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013705PMC
June 2018
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