Long noncoding RNA MALAT1 regulates autophagy associated chemoresistance via miR-23b-3p sequestration in gastric cancer

Molecular Cancer

Lin XiZhou¹  Yu YingCong¹  You Sunwu²  Tong Xiaochun²  Chen Senrui²  Hu YiRen²  Chen Ende²  Li Keqin²  Chen Yanfan³ 

[1] Department of Gastroenterology, The third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital;Department of General Surgery, The third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital;Department of radiology, Wenzhou No.3 Clinical Institute of Wenzhou Medical University, Wenzhou People’s Hospital;

关键词: lncRNA;    MALAT1;    Gastric cancer;    Chemoresistance;    Autophagy;   

DOI  :  10.1186/s12943-017-0743-3

来源: DOAJ

【 摘 要 】

Abstract Background Chemoresistance has long been recognized as a major obstacle in cancer therapy. Clarifying the underlying mechanism of chemoresistance would result in novel strategies to improve patient’s response to chemotherapeutics. Methods lncRNA expression levels in gastric cancer (GC) cells was detected by quantitative real-time PCR (qPCR). MALAT1 shRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate MALAT1 expression. In vitro and in vivo assays were performed to investigate the functional role of MALAT1 in autophagy associated chemoresistance. Results We showed that chemoresistant GC cells had higher levels of MALAT1 and increased autophagy compared with parental cells. Silencing of MALAT1 inhibited chemo-induced autophagy, whereas MALAT1 promoted autophagy in gastric cancer cells. Knockdown of MALAT1 sensitized GC cells to chemotherapeutics. MALAT1 acts as a competing endogenous RNA for miR-23b-3p and attenuates the inhibitory effect of miR-23b-3p on ATG12, leading to chemo-induced autophagy and chemoresistance in GC cells. Conclusions Taken together, our study revealed a novel mechanism of lncRNA-regulated autophagy-related chemoresistance in GC, casting new lights on the understanding of chemoresistance.

【 授权许可】

Unknown