Modulation of cisplatin resistance in gastric cancer by LncRNA SNHG15
2022
Wen-Jie Kong | Wei-Dong Liu | Man Wang | Wen-Jia Hui | Feng Gao
Background: The role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in cisplatin-resistance was studied in gastric cancer. Methods: The relative SNHG15 expression and its correlation with survival were assayed on the Cancer Genome Atlas data and confirmed with the clinical samples we collected. Cisplatin-resistant MKN45 cell line (MKN45 CR) was established. SNHG15 plasmid and SNHG15 shRNA plasmid were transfected into MKN45 cells and MKN45 CR cells. Colony formation analysis and cell counting kit-8 assay were utilized to determine cell proliferation and viability. The binding between SNHG15 and zeste 2 polycomb repressive complex 2 subunit (EZH2) was testified with RNA immunoprecipitation (RIP). The promoter activity of phosphatase and tensin homolog (PTEN) was evaluated by luciferase reporter assay. Results: High SNHG15 expression was correlated with the poor overall survival of gastric cancer patients, and cisplatin treatment can induce time and dose-dependent up-regulation of SNHG15. At the same time, SNHG15 overexpression could promote the cisplatin resistance, while SNHG15 inhibition could diminish the cisplatin resistance. RIP assays confirmed the interaction of SNHG15 with EZH2. More importantly, SNHG15 inhibited PTEN promoter activity by reducing EZH2 recruitment in MKN45 CR cells. Conclusion: SNHG15 epigenetically prohibits PTEN expression by recruiting EZH2 in gastric cancer cisplatin-resistant cells.
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