Depletion of lncRNA MALAT1 inhibited sunitinib resistance through regulating miR-362-3p-mediated G3BP1 in renal cell carcinoma

Abstract

Long non-coding RNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) contributes to chemotherapy resistance in some cancers, but the role of MALAT1 in sunitinib (SU) chemoresistance of carcinoma (RCC) is still unknown. In this study, MALAT1 expression in SUresistance tumor tissues and cells was tested by qRT-PCR. Then, CCK-8, Annexin V-FITC/PI, transwell, and Western blotting assays were used to evaluate cell viability and IC50, apoptosis, cell invasion, and resistance of SU-resistance RCC cells after transfected with small interfering RNA against MALAT1. Further, RNA pull-down and luciferase reporter assay were applied to investigate the underlying mechanism of MALAT1 in SU resistance. The results showed that MALAT1 expression was dramatically upregulated in SU-resistance RCC tissues and cell lines. Knockdown of MALAT1 inhibited proliferation, invasion, and SU chemoresistance, but induced apoptosis in RCC cells. The results of RNA pull-down and luciferase reporter assay indicated that MALAT1 could interact with miR-362-3p and miR-362-3p interact with RasGAP SH3-domain-Binding Protein 1 (G3BP1). Moreover, G3BP1 also played a role in SU chemoresistance of RCC cells, and MALAT1 could perform as a miR-362-3p sponge to modulate G3BP1 expression. Rescue experiments suggested that downregulation of miR-362-3p and overexpression of G3BP1 can reverse the SU chemosensitivity of MALAT1 knockdown in RCC cells. In conclusion, depletion of LncRNA MALAT1 inhibited SU chemoresistance through modulating G3BP1 via sponging miR-362-3p in RCC cells, suggesting that targeting MALAT1 may be a potential therapeutic strategy for SU-resistance RCC.

lncRNA MALAT1 participates in metformin inhibiting the proliferation of breast cancer cell

“…In cisplatin‐resistant ovarian cancer tissues and cells, MALAT1 was reported to be increased and knock‐down of which could decrease cisplatin resistance 17 . In renal cell carcinoma, sunitinib resistance is showed to be positive associated with dramatical up‐regulation of MALAT1, and the chemoresistance could be reversed by MALAT1 knock‐down 18 . Therefore, regulating the expression of MALAT1 would be a valuable means to repurposing metformin in breast cancer treatment.…”

“…17 In renal cell carcinoma, sunitinib resistance is showed to be positive associated with dramatical up-regulation of MALAT1, and the chemoresistance could be reversed by MALAT1 knock-down. 18 Therefore, regulating the expression of MALAT1 would be a valuable means to repurposing metformin in breast cancer treatment.…”

Research Progress on the Structure and Function of G3BP

“…The Y-box binding protein 1 (YBX1) interacts with G3BP1 to upregulate the secreted phosphoprotein 1 (SPP1) and activate NF-kB, which ultimately promotes RCC metastasis (127). G3BP1 enhances the resistance of sunitinibresistance RCC (128). This suggests that targeting G3BP1 may prove to be an effective therapeutic strategy for RCC (129).…”

Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells

“…Recently, a numeral study has explored the fundamental role of MALAT1 in the development of drug resistance in different cancer cells. Some of these include resistance to the hepatocellular carcinoma cells by sponging miR-216b ( Yuan P. et al, 2016 ), sunitinib-resistance by regulating miR-362-3p-mediated G3BP1 in renal cell carcinoma ( Wang Z. et al, 2020 ), cisplatin resistance in gastric cancer ( Dai et al, 2020 ), and docetaxel resistance of prostate cancer cells via miR-145-5p-mediated regulation of AKAP12 ( Xue et al, 2018 ).…”