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

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


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.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Autophagy
  • Autophagy-Related Protein 12 / genetics*
  • Autophagy-Related Protein 12 / metabolism
  • Cell Proliferation
  • Cell Survival
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Transplantation
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Up-Regulation*


  • ATG12 protein, human
  • Antineoplastic Agents
  • Autophagy-Related Protein 12
  • MALAT1 long non-coding RNA, human
  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding