Ribose-5-phosphate isomerase A regulates hepatocarcinogenesis via PP2A and ERK signaling

Shih Ci Ciou, Yu Ting Chou, Yu Ling Liu, Yu Chin Nieh, Jeng Wei Lu, Shiu Feng Huang, Li Hao Cheng, Jeng Fan Lo, Ming Jen Chen, Ming Chi Yang, Chiou Hwa Yuh*, Horng Dar Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


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.

Original languageEnglish
Pages (from-to)104-115
Number of pages12
JournalInternational Journal of Cancer
Issue number1
StatePublished - 1 Jul 2015


  • ERK
  • PP2A
  • aging
  • hepatocellular carcinoma
  • oncogenesis
  • pentose phosphate pathway
  • ribose-5-phosphate isomerase A
  • tumor biomarker


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