Long non‑coding RNA MALAT1 activates autophagy and promotes cell proliferation by downregulating microRNA‑204 expression in gastric cancer

Abstract

Gastric cancer (GC) is one of the major diseases that threaten human health. Although the development of novel drugs has significantly improved the efficacy of GC chemotherapy, the 5-year survival rate of patients with GC remains unsatisfactory. In the present study, the role and mechanism of the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in GC proliferation was investigated. Clinical specimens and cancer cells were analyzed by western blotting or immunofluorescence. Reverse transcription-quantitative polymerase chain reaction analysis of 57 paired GC and non-tumorous tissues revealed elevated expression of MALAT1 in GC tissues compared with controls. In addition, increased MALAT1 was associated with elevated levels of microtubule-associated protein 1 light chain 3β (LC3B) and antigen Ki67, which are autophagy and proliferation markers, respectively. MTT and colony formation assay results demonstrated that MALAT1 promoted GC cell proliferation. To the best of our knowledge, the present study was the first to demonstrate that upregulated MALAT1 was associated with increased autophagy activation in GC tissues. Furthermore, this study reported that MALAT1 increased cell proliferation and enhanced autophagy activation in GC cells. In addition, the results revealed that MALAT1 inhibited microRNA (miR)-204 expression in GC cells. The present study also demonstrated that miR-204 repressed autophagy through the downregulation of LC3B and transient receptor potential melastatin 3 expression in GC cells. These results indicated that MALAT1 activated autophagy and promoted cell proliferation by downregulating miR-204 expression in GC.

<p>Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression</p>

“…[12][13][14] An increasing number of studies have shown that numerous lncRNAs are abnormally expressed in GC. [15][16][17] Notably, there is increasing evidence supporting a close relationship between lncRNA dysregulation and malignant characteristics in GC. 18,19 MicroRNAs (miRNAs, miRs) are classified as singlestranded noncoding short RNAs approximately 19-25 nucleotides in length.…”

Autophagy-Related Long Non-coding RNA Is a Prognostic Indicator for Bladder Cancer

“…In acute myeloid leukemia, lncRNA UCA1 promotes autophagy by targeting miR-96-5p ( 35 ). lncRNA MALAT1 activates autophagy and promotes the cell proliferation by downregulating the miRNA-204 expression in gastric cancer ( 36 ). However, to-date, there has been no systematic and comprehensive analysis of autophagy-related lncRNA in BC.…”

Prognostic model based on autophagy-related lncRNAs in gastric cancer

“…Among them, some lncRNAs were de ned as protective factors while others were risk factors [25,[41][42][43][44]. Furthermore, several studies have proved that lncRNAs participated in the progression, especially malignant progression of GC through regulating autophagy-related mRNAs [24][25][26][27][28][29]45].…”

“…Pieces of evidence showed that lncRNA is vital for the occurrence, prognosis, and chemoresistance of GC by regulating autophagy-related mRNA [24][25][26]. Some studies have demonstrated that silencing of LINC01419 and CCAT2 promotes autophagy through constraining the PI3K/Akt1/mTOR pathway thus inhibiting the invasion and migration of GC cells [27,28]; Another study also revealed that autophagy was associated with the proliferation of GC cells, partially due to the MALAT1 promoted by downregulating miR-204 [29]. However, most of these experiments only explored the role of one or a few lncRNAs in the autophagy of GC, and could not fully explain the relevant mechanisms.…”