title: Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4.
abstract: Many tumors metabolise the majority of the glucose that they take up through glycolysis even in the presence of an adequate oxygen supply. Lactate dehydrogenase A (LDH-A) is the critical enzyme that catalyses the transformation of pyruvate to lactate. We demonstrate that LDH-A reduction can suppress the tumorigenicity of intestinal-type gastric cancer (ITGC) cells by downregulating Oct4 both in vitro and in vivo. A statistical analysis of 661 ITGC specimens showed a significant correlation between LDH-A and Oct4 expression. Moreover, patients with low LDH-A/negative Oct4 expression exhibited better overall survival than patients with other combinations. We conclude that the close correlation of LDH-A and Oct4 may offer a promising therapeutic strategy for ITGC.
authors.affiliation: Department of Oncology, Changzheng Hospital, Shanghai, China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Guanzhen
authors.initials: G
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Pan
authors.forename: Jiejun
authors.initials: J
authors.lastname: Wang
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D016086:Lentivirus / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D007527:Isoenzymes; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1