Dataset Information

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 SU-resistance 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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7469516 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets