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

Abstract

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 IC 50 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.

Expression of MALAT1 Promotes Trastuzumab Resistance in HER2 Overexpressing Breast Cancers

“…Furthermore, MALAT1-mediated tumor metastasis has been associated with chemoresistance in gastric, lung, cervical, ovarian, and colorectal cancers, and the underlying mechanisms were associated with different cell signaling pathways [ 27 , 28 , 29 , 50 , 51 , 52 ]. High expression of MALAT1 decreased cisplatin sensitivity in lung cancer, and the mechanism is associated with upregulated Multidrug resistance-associated protein 1 (MRP1) and Multi-Drug resistance 1 (MDR1) via STAT3 [ 50 ].…”

“…Signaling pathways associated with MALAT1-induced cell proliferation and metastasis include the phosphatidylinositol-3-kinase/serine/threonine kinase (PI3K) and protein kinase B (Akt) pathway [ 27 , 28 , 29 ]. MALAT1 has been shown to regulate cell proliferation and cisplatin resistance via the PI3K/Akt pathway in cervical and gastric cancer [ 27 , 28 , 29 ]. It has also been reported to promote cell proliferation and epithelial-to-mesenchymal transition (EMT) via PI3K/AKT pathway in epithelial ovarian cancer [ 29 ].…”

Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma

“…High expression of both proteins has been correlated to a decreased sensitivity in vitro [148], and a less satisfactory outcome in patients with advanced GAC treated with adjuvant chemotherapy [139]. Increased activity of PI3K/AKT and JAK/STAT3 pathways has also been related to a lower response of these patients to cisplatin [143] or trastuzumab [145].…”

<p>Long Non-Coding RNA NCK1-AS1 Serves an Oncogenic Role in Gastric Cancer by Regulating miR-137/NUP43 Axis</p>

“…Li et al multiple lncRNAs were found to be abnormally expressed in GC through inhibiting or stimulating cellular malignant behaviors. [14][15][16] Dai et al reported lncRNA MALAT1 contributes the response of GC cells to cisplatin via regulating PI3K/AKT pathway. 14 Shi et al found that LINC00152 inhibits GC cell migration and invasion through alteration of the ERK/MAPK signaling pathway.…”

“…[14][15][16] Dai et al reported lncRNA MALAT1 contributes the response of GC cells to cisplatin via regulating PI3K/AKT pathway. 14 Shi et al found that LINC00152 inhibits GC cell migration and invasion through alteration of the ERK/MAPK signaling pathway. 15 Wei et al revealed that increased expression of lncRNA HOTAIR stimulates GC growth by upregulating COL5A1 via sponging miR-1277-5p.…”