ORIGINAL ARTICLE Cell Research (2009): 1150-1164 Bystin-like protein is upregulated in hepatocellular carcinoma and required for nucleologenesis in cancer cell proliferationHanzhi Wang1,2, Wei Xiao3, Qinbo Zhou1,2, Yun Chen4, Shuo Yang1, Jiansong Sheng1, Yanqing Yin2, Jia Fan5 and Jiawei Zhou1,2 1Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology2State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3Department of Pathology, First People's Hospital, Taizhou, Jiangsu 225300, China 4Department of Pathology, No. 411 Hospital, Shanghai 200081, China 5Key Laboratory for Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China
The bystin-like (BYSL) gene was previously characterized to encode an accessory protein for cell adhesion that participates in early embryo implantation. It is also involved in 40S ribosomal subunit biogenesis and is found to be expressed in rapidly growing embryo and cancer cell lines. In order to explore the role of BYSL in cancer cell proliferation and growth, we used hepatocellular carcinoma (HCC) as a model. Here, we report that BYSL is crucial for HCC cell growth both in vitro and in vivo. Expression levels of BYSL mRNA and protein in human HCC specimens were markedly increased compared with those seen in adjacent non-cancerous tissue. In vitro, inhibition of BYSL by short hairpin RNA decreased HCC cell proliferation, induced apoptosis and partially arrested the cell cycle in the G2/M phase. In vivo, HCC cells treated with BYSL siRNA failed to form tumors in nude mice after subcutaneous implantation. To determine the cellular basis for BYSL RNAi-induced cell growth arrest, BYSL subcellular localization in mitotic and interphase HepG2 cells was examined. BYSL was present at multiple stages during nucleologenesis, including in nucleolus-derived foci (NDF), perichromosomal regions and the prenucleolar body (PNB) during mitosis. BYSL depletion remarkably suppressed NDF and PNB formation, and disrupted nucleoli assembly after mitosis, resulting in increased apoptosis and reduced tolerance of HCC cells to serum starvation. Taken together, our studies indicate that upregulated BYSL expression plays a role in hepatocarcinogenesis. Cell Research (2009) 19:1150–1164. doi: 10.1038/cr.2009.99; published online 18 August 2009 Keywords: Bystin-like, nucleologenesis, nucleolar proteins, cell growth, hepatocellular carcinoma |
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