Open AccessMiR‐5683 suppresses glycolysis and proliferation through targeting pyruvate dehydrogenase kinase 4 in gastric cancer
Author(s) -
Miao Yongchang,
Li Qing,
Sun Guangli,
Wang Lu,
Zhang Diancai,
Xu Hao,
Xu Zekuan
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3344
Subject(s) - oncogene , transfection , cancer research , cell growth , pdk4 , apoptosis , biology , microrna , pyruvate dehydrogenase complex , pyruvate dehydrogenase kinase , microbiology and biotechnology , pyruvate kinase , cell cycle , glycolysis , cell culture , gene , biochemistry , enzyme , genetics
Gastric cancer (GC) is one of the most deadly malignancies at global scale, and is particularly common in eastern Asia. MicroRNA‐5683 (miR‐5683) was confirmed to be downregulated in GC by analyzing data from the Cancer Genome Atlas. We packaged miR‐5683‐mimics and miR‐5683‐inhibitors into lentivirus vectors and transfected them into GC cells. MiR‐5683 expression and possible target genes were detected by employing quantitative real‐time polymerase chain reaction. In vitro, cell proliferation and apoptosis were analyzed using CCK‐8, colony formation assay, and flow cytometric assay. We verified the direct interaction between miR‐5683 and the possible downstream target gene pyruvate dehydrogenase kinase 4 (PDK4) through luciferase reporter assay. The role of miR‐5683 in vivo was explored by injecting stably transfected GC cells subcutaneously into nude mice. Here we show that miR‐5683 was downregulated in GC and the decreased level of miR‐5683 enhances GC cell proliferation and impairs apoptosis. Tumor oncogene PDK4, which is associated with GC overall survival and disease‐free survival, has been identified as the target gene of miR‐5683. Besides, we demonstrate that the inhibition of miR‐5683 promotes glycolysis by upregulating the PDK4 expression, thus leading to GC progression. Our study determines that miR‐5683 represses GC glycolysis and progression through targeting PDK4. MiR‐5683 overexpression may thus become a new treatment strategy for GC.