LncRNA SNHG6 knockdown inhibits cisplatin resistance and progression of gastric cancer through miR-1297/BCL-2 axis

Abstract

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelia-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were upregulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment.  Keywords: Gastric cancer, cisplatin resistance, lncRNA SNHG6, miR-1297, BCL-2

LncRNA SNHG6 sponges miR-101 and induces tamoxifen resistance in breast cancer cells through induction of EMT

“…Our hypothesis to focus on SNHG6 for this study was based on the published literature supporting a role of SNHG6 in cancer drug resistance, coupled with the fact that its role specifically in tamoxifen resistance has never been elucidated. As per the published literature, SNHG6 can impact cisplatin resistance in gastric cancer (15,26), 5-FU resistance in colorectal cancer (14), paclitaxel resistance in prostate cancer (16) as well as radioresistance in cervical cancer (13). We now provide first evidence for a role of lncRNA SNHG6 in drug resistance of breast cancer, in general, and tamoxifen resistance, in particular.…”

“…It would also be of interest to readers to know that we combined the information from published literature as well as bioinformatics analysis to shortlist the potential miRNAs that can be sponged by SNHG6. miR-26a (14), miR-186 (16), miR-325 (15), miR-485 (13) and miR-1297 (26) represent miRNAs that were shortlisted based on published reports while let-7d/e and miR-101 represent miRNAs that were identified through DIANA-LncBase v3 platform.…”

Clinical application and detection techniques of liquid biopsy in gastric cancer

“…Cisplatin (CDDP) chemotherapy significantly reduces the level of miR-30a in GC cells, and interestingly, up-regulation of miR-30a inhibits GC cell sensitivity to CDDP [164]. Furthermore, CDDP-resistant GC cells that up-regulated SNHG6 and circ_AKT3 expression could regulate CDDP Interaction with miR-206 regulates cisplatin resistance [168] resistance and GC progression via sponge miR-1297 and miR-206, respectively, indicating that targeting SNHG6 and circ_AKT3 may be a promising option to address GC chemoresistance [166,168]. In 5-fluorouracil (5-FU)resistant GC cells, hsacirc_004413 could make GC cells resistant to 5-FU by adsorbing miR-145-5p [167].…”

Epithelial-mesenchymal transition-related long noncoding RNAs in gastric carcinoma

“…SNHG6 positively regulates B-Cell Lymphoma 2 (BCL-2) by sponging miR-1297. The DDP resistance, proliferation, and metastasis of DDP-resistant cells can be suppressed by depletion of SNHG6 ( Mei et al, 2021 ). Exosome HOTTIP can regulate the miR-218/high-mobility group A1 (HMGA1) axis, contributing to cisplatin resistance in GC cells.…”