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

Xi,Zhiwen; Si,Jinchun; Nan,Jun

doi:10.3892/ijo.2018.4609

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

Authors:
- Zhiwen Xi
- Jinchun Si
- Jun Nan
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Affiliations: Department of Gastroenterology, The First People's Hospital of Shangqiu, Shangqiu, Henan 476100, P.R. China, Department of Surgical Teaching and Research, Shangqiu Medical College, Shangqiu, Henan 476100, P.R. China
Published online on: October 26, 2018 https://doi.org/10.3892/ijo.2018.4609
Pages: 239-248

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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.

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