Abstract

MicroRNAs (miRs) are considered to be tumor suppressors or oncogenes as they regulate cell proliferation, migration, invasion, and differentiation. Recently, microRNA-505 (miR-505) has been reported as being involved in the progression of several human cancers. In the present study, we aim to investigate the expression rate and functional role of miR-505-5p in cervical cancer (CC) to determine its significance regarding the disease’s development.The expression of miR-505-5p and cyclin-dependent kinase 5 (CDK5) in specimens of patients with CC and CC cell lines was examined by quantitative real-time PCR (qRT-PCR) and Western Blot. The relationship between miR-505-5p and CDK5 was verified by luciferase reporter assay. Cell counting kit-8 (CCK-8) assay, Scratch wound healing assay and transwell assay were used to detect the roles of miR-505-5p and CDK5 in CC cell functions. Western Blot was utilized to explore the epithelial–mesenchymal transition (EMT) markers.The result showed that in CC tissues and CC cell lines miR-505-5p was down-regulated while CDK5 level was up-regulated. MiR-505-5p was closely correlated with the metastasis-associated clinicopathological features. Overexpression of miR-505-5p inhibited cell viability, cell metastasis and EMT in CC cells. CDK5 was confirmed as a direct target of miR-505-5p and inverse relationship between them was also observed. Overexpression of CDK5 reduces the inhibitory effects of miR-505-5p in CC.Taken together, these results determine that miR-505-5p is a tumor suppressor miRNA which regulates tumor cell proliferation, migration, and invasion via binding to the functional target CDK5 and demonstrates its potential for future use in the treatment of CC.

Highlights

  • According to statistics generated by the American Cancer Society in 2015, the fatality rate of cervical cancer (CC) is the second highest among female patients [1]

  • MiR-505-5p is down-regulated in human CC tissue samples and correlates with poor prognosis in patients with cervical cancer

  • Our findings showed associations between miR-505-5p expression with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.016), tumor size (P=0.034), lymph node metastasis (P=0.019), and histology grade (P=0.020) in patients with CC (Table 1)

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Summary

Introduction

According to statistics generated by the American Cancer Society in 2015, the fatality rate of cervical cancer (CC) is the second highest among female patients [1]. CC is ranked 9th of all cancers in terms of mortality, and accounts for 266,000 deaths/year worldwide. The highest new CC incidence rate in 2012 was in South-Central Asia (151.8/100,000), which had the world’s highest estimated number of cancer deaths of 82.2/100,000 [2]. Despite considerable advances in treatment, the 5-year survival rate for cervix uteri cancers varies, from below 40% to more than 70% across different countries [3–5]. It is essential to investigate the mechanisms involved, and to identify new molecular markers for personalized treatment leading to advances in CC therapy

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