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

Abstract

BackgroundChemoresistance 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.MethodslncRNA 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.ResultsWe 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.ConclusionsTaken together, our study revealed a novel mechanism of lncRNA-regulated autophagy-related chemoresistance in GC, casting new lights on the understanding of chemoresistance.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0743-3) contains supplementary material, which is available to authorized users.

Long non‐coding RNA MIF‐AS1 promotes gastric cancer cell proliferation and reduces apoptosis to upregulate NDUFA4

“…Liu et al showed the tumor‐promoting role of HOTAIR in gastric cancer progression through positively regulating HER2 expression by sponging miR‐331‐3p. In addition, expression of several miRNAs, including miR‐675, miR‐145‐5p, miR‐152, miR‐145, miR‐23b‐3p, and miR‐335‐5p, are significantly dysregulated by lncRNAs and then change the expression of target mRNAs in gastric cancer.…”

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

“…It is widely reported that lncRNAs are involved in multiple malignant tumors including OS . Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is located at chromosome 11q13.1 and is discovered as a new cancer‐associated lncRNAs in various cancers . Wang Y found that MALAT1 promoted OS cell metastasis and proliferation via serving as a ceRNA of ROCK1 and ROCK2 .…”

“…[17][18][19][20][21][22] Metastasisassociated lung adenocarcinoma transcript 1 (MALAT1) is located at chromosome 11q13.1 and is discovered as a new cancer-associated lncRNAs in various cancers. [23][24][25][26] Wang Y found that MALAT1 promoted OS cell metastasis and proliferation via serving as a ceRNA of ROCK1 and ROCK2. 21 Luo W illustrated that MALAT1 contributed to an increased expression of transforming growth factor alpha (TGFA) and facilitated OS cell growth through an inhibition of miR-376a.…”

Differential expression profiling of lncRNAs related to Epstein‐Barr virus infection in the epithelial cells

“…On the contrary, lncRNA expression is relatively tissue‐specific, and studies have shown that one lncRNA may play different roles by targeting different pathways in different cell types. For example, the lncRNA MALAT1 plays different roles by regulating different miRNAs and pathways in GC, colon cancer, and retinoblastoma …”

“…For example, the lncRNA MALAT1 plays different roles by regulating different miRNAs and pathways in GC, colon cancer, and retinoblastoma. [45][46][47] A comprehensive database that provides the functions of lncRNAs and their target genes is still lacking. Therefore, it is essential to use online software and databases to predict lncRNA interactions, cooperation, localization, and function.…”