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Mol Cancer. 2017 Nov 21;16(1):174. doi: 10.1186/s12943-017-0743-3.

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

Author information

1
Department of General Surgery, The third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
2
Department of Gastroenterology, The third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
3
Institute of Gastroenterology, Zhejiang University(IGZJU), Hangzhou, Zhejiang, China.
4
Department of radiology, Wenzhou No.3 Clinical Institute of Wenzhou Medical University, Wenzhou People's Hospital, No. 57 Canghou Street, Wenzhou, Zhejiang, 325000, China. chenyanfan8659@sina.com.

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.

KEYWORDS:

Autophagy; Chemoresistance; Gastric cancer; MALAT1; lncRNA

PMID:
29162158
PMCID:
PMC5699172
DOI:
10.1186/s12943-017-0743-3
[Indexed for MEDLINE]
Free PMC Article

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