LncRNA MALAT1 potentiates autophagy-associated cisplatin resistance by regulating the microRNA-30b/autophagy-related gene 5 axis in gastric cancer

Abstract

Gastric cancer (GC) is the fourth most common type of cancer worldwide and chemoresistance is a major obstacle to successful GC treatment. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to measure the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA (miR)-30b. Western blot analysis was conducted to detect the protein expression of autophagy-related gene 5 (ATG5), p62 and LC3 (LC3-I and LC3-II). Cell viability and half maximal inhibitory concentration were determined by the Cell Counting Kit-8 assay. The green fluorescent protein (GFP)-LC3-positive cell percentage was determined by the GFP-LC3 puncta experiment. Luciferase reporter and RNA immunoprecipitation assays were used to explore the molecular associations among MALAT1, miR-30b and ATG5. MALAT1 was found to be highly expressed in CDDP-resistant AGS(AGS/CDDP) cells and CDDP-resistant HGC-27 (HGC-27/CDDP) cells. Cell viability was markedly increased in MALAT1-overexpressing AGS/CDDP cells, but was notably reduced in MALAT1-depleted HGC-27/CDDP cells. Moreover, MALAT1 potentiated CDDP resistance by facilitating autophagy in AGS/CDDP and HGC-27/CDDP cells. Further investigations demonstrated that MALAT1 inhibited miR-30b expression by direct interaction. Moreover, miR-30b abolished MALAT1-induced CDDP resistance by inhibiting autophagy in AGS/CDDP and HGC-27/CDDP cells. Furthermore, ATG5 was found to be a target of miR-30b. miR-30b weakened resistance to CDDP by inhibiting autophagy in AGS/CDDP and HGC-27/CDDP cells, while this effect was abrogated by increased ATG5 expression. Additionally, MALAT1 sequestered miR-30b from ATG5 to increase ATG5 expression in AGS/CDDP and HGC-27/CDDP cells. Therefore, MALAT1 potentiated autophagy-related CDDP resistance through suppressing the miR-30b/ATG5 axis in AGS/CDDP and HGC-27/CDDP cells, indicating that it may represent a promising target for the reversal of chemoresistance in GC.