MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B

详细信息    查看全文

• 作者：Guo Li¹ ; Yong Liu¹ ; Zhongwu Su ; Shuling Ren ; Gangcai Zhu ; Yongquan Tian ; Yuanzheng Qiu ; ^{xyqyz@hotmail.com}
• 关键词：Nasopharyngeal carcinoma ; Radioresistance ; MicroRNA ; miRNA-324-3p ; WNT2B
• 刊名：European Journal of Cancer
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：49
• 期：11
• 页码：2596-2607
• 全文大小：2710 K

文摘

Purpose

Radioresistance severely restricts the clinical treatment of nasopharyngeal carcinoma (NPC). Accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer progression and sensitivity to radiation. Therefore, we aimed to identify miRNAs associated with radioresistance in NPC.

Methods

Aberrant miRNA-324-3p expression in NPC CNE-2 cells with radioresistance (CNE-2-Rs), compared to its parental cells, was screened by high-throughput sequencing technology and determined by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) analysis. Bioinformatic analysis was used to predict the downstream target genes of miRNA-324-3p. Then, functional and mechanical analyses of miRNA-324-3p in NPC radioresistance were performed by overexpression and down-regulation of miRNA-324-3p in CNE-2-Rs cells and its parental cells. Finally, the clinical significance of miRNA-324-3p and WNT2B was investigated in NPC tissues.

Results

Our data reveal that the expression of miRNA-324-3p is significantly decreased in CNE-2-Rs cells compared to its parental cells, and WNT2B is predicted to be the downstream target of miRNA-324-3p. Both overexpression and down-regulation of miRNA-324-3p following irradiation result in radiosensitivity alterations and protein changes of WNT2B signalling pathway in CNE-2-Rs cells and its parental cells. Importantly, down-regulation of miRNA-324-3p and up-regulation of WNT2B are significantly correlated with advanced clinical stages of NPC and this inverse expression pattern is also observed in NPC tissues before and after irradiation.

Conclusions

The present study reveals that miRNA-324-3p contributes to the radioresistance of NPC by regulating the WNT2B signalling pathway. Both miRNA-324-3p and WNT2B are potential biomarkers for radioresistance in NPC, which may serve as valuable targets for reversing radioresistance in the management of NPC.