Abstract

We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined. Bmi-1 was confirmed as a target of miRNA-132. Survival was higher and apoptosis lower in the miR-132 inhibitor group than the blank group after various doses of radiation. By contrast, survival was lower and apoptosis higher in the miRNA-132 mimics and siBmi-1 groups than in the blank group. Moreover, miR-132 expression increased and Bmi-1 mRNA expression decreased in each group at radiation doses of 6 and 8 Gy. Finally, co-administration of radiotherapy and exogenous miR-132 inhibited the growth of HeLa cell transplant-induced tumors in nude mice more effectively than radiotherapy alone. These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.

Highlights

  • Cervical cancer (CC) has a high death rate and is the third most common type of cancer worldwide [1]

  • We investigated the mechanism by which the miRNA miR-132 affects the radiosensitivity of HeLa, SiHa, and C33A cervical cancer cells via regulation of Bmi-1 expression

  • Our results indicate that miR-132 was down-regulated in cervical cancer tissues and that its expression increased as radiation intensity increased

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Summary

Introduction

Cervical cancer (CC) has a high death rate and is the third most common type of cancer worldwide [1]. It is estimated that over 529,000 people are diagnosed with cervical cancer every year, with most cases occurring in developing countries. In China, over 58,000 new patients are diagnosed with, and more than 20,000 people die from, CC each year [2]. Radio-chemotherapy, radical hysterectomy, and radiotherapy with cisplatin are the most commonly used treatments for nonsurgical, early-stage, and late-stage CC patients, respectively [3]. Radioresistance in CC cells contributes to poor prognosis in patients [4] and is the main obstacle to successful radiotherapy treatment [5]. The mechanisms underlying radiosensitivity in CC cells remain unknown [6]

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