rs61991156 in miR-379 is associated with low capability of glycolysis of gastric cancer by enhanced regulation of PKM2

Cancer Cell International - Tập 18 - Trang 1-8 - 2018
Na Cao1, Meng Li2, Jun Han2, Yongren Wang3, Xiaowei Wang2
1Department of Medical Affairs, Nanjing Center Hospital, Nanjing, China
2Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
3Department of Hematology and Oncology, Children’s Hospital of Nanjing Medical University, Nanjing, China

Tóm tắt

Glycolysis is an important metabolic oncogenic change also play a pivot role in the Warburg effect. Glycolysis related gene PKM2 expressed differently individually. Presently, we sought to investigate the effect of single nucleotide polymorphism (SNP) at rs61991156 of miR-379 on gastric cancer (GC) proliferation and metabolism. The genotype of rs61991156 in miR-379 was investigated by using real-time PCR. The glycolysis-related metabolites were determined by using GC–TOF–MS. The biological effects of rs61991156 in miR-379 was explored by in vitro studies. In this study, we found that rs61991156 in miR-379 was involved in the occurrence of GC by acting on the 3′UTR region of PKM2. The clinical data analysis revealed that A > G in rs187960998 was significantly associated with better differentiation, small tumor size, and non-metastasis. In vitro study further revealed that A > G SNP of miR-379 could decrease GC cell proliferation as well as the promoter activity and expression of PKM2. The glycolysis of the patients with miR-379 GG genotype was significantly lower than AG and AA genotype by metabolomics analysis. The patients with AA genotype have significantly lower PKM2 expression compared to the G carrier, while there is no significant expression difference in miR-379 expression. Patients with AA genotype have significantly shorter survival rate compared to the G carrier. rs61991156 in miR-379 was highly associated with a decreased risk, well differentiation and better post-surgery survival in Chinese population by inhibiting the expression of PKM2.

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