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LncRNA MALAT1 Regulates the Cell Proliferation and Cisplatin Resistance in Gastric Cancer via PI3K/AKT Pathway

Authors Dai Q, Zhang T, Li C

Received 26 December 2019

Accepted for publication 2 March 2020

Published 13 March 2020 Volume 2020:12 Pages 1929—1939

DOI https://doi.org/10.2147/CMAR.S243796

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Seema Singh


Qingqiang Dai, Tianqi Zhang, Chen Li

Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China

Correspondence: Chen Li
Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China
Tel +86-21-64670644
Fax +86-21-64393909
Email leedoctor@sina.com

Background: Many studies showed that long non-coding RNA MALAT1 is served as an oncogene. However, the specific role of MALAT1 in gastric cancer is not fully elucidated. The aim of this study is to elucidate the regulatory effects of MALAT1 on tumor development and cisplatin resistance in gastric cancer.
Methods: TCGA database was applied to investigate the expression levels of MALAT1 in GC tissues and normal gastric tissues and its correlation with GC patients’ survival. Univariate and multivariate analysis were performed to investigate whether MALAT1 expression is an independent risk for overall survival of gastric cancer patients. The expression of MALAT1 was detected by Quantitative real-time PCR. After knockdown or overexpression of MALAT1, the cellular functions of GC cells were detected by cell-proliferation, flow cytometry, transwell assay and colony formation assays, respectively. Western blot analysis was performed to detect the protein levels of Bcl-2 and key genes in the PI3K/AKT pathway in GC cells. Finally, CCK-8 assay was performed to explore the effect of MALAT1 on cisplatin resistance of GC cells.
Results: Higher expression of MALAT1 was detected in GC tissues than that of adjacent normal tissues, high MALAT1 expression is an independent risk for overall survival of gastric cancer patients. Knockdown of MALAT1 inhibited proliferation, migration and invasion of GC cells, while overexpression of MALAT1 Overexpression of MALAT1 yielded opposite results. Western blot results showed that protein expressions of p-PI3K, p-AKT and p-STAT3 were downregulated after MALAT1 knockdown in GC cells, while these proteins were upregulated after MALAT1 overexpression. Additionally, the IC50 in MGC803/CDDP cells transfected with si-MALAT1 was lower than in those transfected with si-NC. The apoptotic rate in MGC803 cells transfected with pcDNA-MALAT1 was remarkably lower than those transfected with NC.
Conclusion: We demonstrated that MALAT1 is highly expressed in GC, high MALAT1 expression is an independent risk factor for OS among GC patients. Moreover, MALAT1 promotes malignant progression of GC and contributes to cisplatin resistance of GC cells, indicating MALAT1 may serve as a biological hallmark for predicting the prognosis of GC.

Keywords: gastric cancer, MALAT1, proliferation, migration and invasion, cisplatin resistance

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