Home HOME Neoplasma 2020 Neoplasma Vol.67, No.5, p.1114–1121, 2020

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.67, No.5, p.1114–1121, 2020

Title: miR-15a-5p targets PHLPP2 in gastric cancer cells to modulate platinum resistance and is a suitable serum biomarker for oxaliplatin resistance
Author: K. Pang, J. Song, Z. Bai, Z. Zhang

Abstract: MicroRNAs can bind with target genes thus inhibiting their expression levels to regulate cell survival, hence serve as serum biomarkers for a variety of purposes. Our aim was to explore the role of miR-15a-5p in the cisplatin/oxaliplatin resistance of gastric cancer. In this study, the growth and apoptosis of gastric cancer cell lines were measured with cell viability assay and flow cytometry, respectively. Dual-luciferase assay was applied for miRNA target validation. Expression of PHLPP2 and miR-15a-5p were measured by quantitative polymerase chain reaction and western blot, respectively. Serum miR-15a-5p level of 82 gastric cancer patients was examined by qPCR. Our results indicated that miR-15a-5p overexpression increased cisplatin resistance of gastric cancer cells, whereas miR-15a-5p downregulation decreased the resistance. miR-15a-5p directly targets and inhibits PHLPP2 in gastric cancer cells, enhancing downstream Akt phosphorylation. Moreover, overexpression of miR-15a-5p could attenuate the decrease in cisplatin resistance induced by PHLPP2 overexpression. Additionally, we observed that lower serum miR-15a-5p level was significantly correlated with better response to oxaliplatin-based chemotherapy as well as better 3-year survival. In conclusion, miR-15a-5p was recognized as a biomarker for platinum resistance and prognosis in gastric cancer, interference of which may be a promising strategy for sensitizing gastric cancer to platinum drugs.

Keywords: gastric cancer, platinum resistance, miR-15a-5p, PHLPP2, biomarker
Published online: 22-Jun-2020
Year: 2020, Volume: 67, Issue: 5 Page From: 1114, Page To: 1121

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