title: Ribose-5-phosphate isomerase A regulates hepatocarcinogenesis via PP2A and ERK signaling.
abstract: The deregulated nonoxidative pentose phosphate pathway (PPP) is known to promote oncogenesis, but the molecular mechanism remains unknown. Here, we report that human ribose-5-phosphate isomerase A (RPIA) plays a role in human hepatocellular carcinoma (HCC). A significant increase in RPIA expression was detected both in tumor biopsies of HCC patients and in a liver cancer tissue array. Importantly, the clinicopathological analysis indicated that RPIA mRNA levels were highly correlated with clinical stage, grade, tumor size, types, invasion and alpha-fetoprotein levels in the HCC patients. In addition, we demonstrated that the ability of RPIA to regulate cell proliferation and colony formation in different liver cancer cell lines required ERK signaling as well as the negative modulation of PP2A activity and that the effects of RPIA could be modulated by the addition of either a PP2A inhibitor or activator. Furthermore, the xenograft studies in nude mice revealed that the modulation of RPIA in liver cancer cells regulated tumor growth and that NIH3T3 cells overexpressing RPIA exhibited increased proliferation, enhanced colony formation, elevated levels of p-ERK1/2 and accelerated tumor growth. This study provides new insight into the molecular mechanisms by which RPIA overexpression can induce oncogenesis in HCC. Furthermore, it suggests that RPIA can be a good prognosis biomarker and a potential target for HCC therapy.
authors.affiliation: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Shih-Ci
authors.initials: SC
authors.lastname: Ciou
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Liu
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Nieh
authors.forename: Jeng-Wei
authors.initials: JW
authors.lastname: Lu
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chou
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Cheng
authors.forename: Jeng-Fan
authors.initials: JF
authors.lastname: Lo
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Chen
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Yang
authors.forename: Chiou-Hwa
authors.initials: CH
authors.lastname: Yuh
authors.forename: Horng-Dar
authors.initials: HD
authors.lastname: Wang
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D054648:Protein Phosphatase 2 / Q000378:metabolism
chemical_list: D054648:Protein Phosphatase 2; D019747:Aldose-Ketose Isomerases; C022548:ribosephosphate isomerase
keywords: ERK; PP2A; aging; hepatocellular carcinoma; oncogenesis; pentose phosphate pathway; ribose-5-phosphate isomerase A; tumor biomarker