title: Rpb3 promotes hepatocellular carcinoma through its N-terminus.
abstract: The expression of RNA polymerase II subunit 3 (Rpb3) was found frequent up-regulation in Hepatocellular carcinoma (HCC) tumors. Significant associations could also be drawn between increased expressions of Rpb3 and advance HCC staging and shorter disease-free survival of patients. Overexpression of Rpb3 increased HCC cell proliferation, migratory rate and tumor growth in nude mice, whereas suppression of Rpb3 using shRNA inhibited these effects. For mechanism study, we found that Rpb3 bound directly to Snail, downregulated E-cadherin, induced HCC cells epithelial-mesenchymal transition (EMT). In particular, N-terminus of Rpb3 blocked Rpb3 binding to Snail, inhibited Rpb3-high-expression HCC cells proliferation, migration, tumor growth in nude mice, and also inhibited DEN-induced liver tumorigenesis. Furthermore, N-terminus of Rpb3 did not inhibit normal liver cells or Rpb3-low-expression HCC cells proliferation. These findings suggest that N-terminus of Rpb3 selectively inhibits Rpb3-high-expression HCC cells proliferation. N-terminus of Rpb3 may be useful in treating patients diagnosed with Rpb3-high-expression HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Zhe-Ping
authors.initials: ZP
authors.lastname: Fang
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Bei-Ge
authors.initials: BG
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Fa-Biao
authors.initials: FB
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Ai-Dong
authors.initials: AD
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Ji
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Yong-Fu
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Institute of Cell Biology, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Li
authors.affiliation: Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China.
authors.forename: Hai-Xiong
authors.initials: HX
authors.lastname: Han
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011485:Protein Binding / Q000235:genetics; D034622:RNA Interference; D012319:RNA Polymerase II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015820:Cadherins; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C491783:POLR2C protein, human; D012319:RNA Polymerase II