title: Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma.
abstract: OBJECTIVE
  Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated.
  
  
  METHODS
  MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer.
  
  
  RESULTS
  Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9.
  
  
  CONCLUSIONS
  These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.
authors.affiliation: Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Wang
authors.forename: Lixia
authors.initials: L
authors.lastname: Xu
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wu
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Tang
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Weijia
authors.initials: W
authors.lastname: Fan
authors.forename: Huiling
authors.initials: H
authors.lastname: Huang
authors.forename: Xinquan
authors.initials: X
authors.lastname: Gu
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D034622:RNA Interference; D000067492:RNAi Therapeutics; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Apoptosis; Invasion; Lactate dehydrogenase A; Migration; Renal cell carcinoma