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

*此作品的通信作者

研究成果: Article同行評審

39 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)104-115
頁數12
期刊International Journal of Cancer
137
發行號1
DOIs
出版狀態Published - 1 7月 2015

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