Abstract

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.

Highlights

  • Cervical cancer is one of the most common gynecologic cancers worldwide with an estimated 527,600 cases and 254,700 deaths according to the GLOBOCAN 2012 data [1]

  • 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 [5]

  • The status of MCM5 mRNA and protein has been found overexpressed in cervical adenocarcinoma tissues and cell lines in our previous study [5]

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Summary

Introduction

Cervical cancer is one of the most common gynecologic cancers worldwide with an estimated 527,600 cases and 254,700 deaths according to the GLOBOCAN 2012 data [1]. The increasing trend of incidence and mortality of cervical cancer was observed in Chinese Cancer Statistics, which reported that there are approximately 98,900 new cervical cancer cases and 30,500 deaths due to cervical cancer in 2015 [2]. Due to aggressive phenotype and radiotherapy resistance, the prognosis of cervical adenocarcinoma is unsatisfactory [4]. 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 [5]. MCM5 may serve as a potential therapeutic target for cervical adenocarcinoma

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