Rpb3 promotes hepatocellular carcinoma through its N-terminus

// Zhe-Ping Fang 1, # , Bei-Ge Jiang 2, # , Fa-Biao Zhang 1, # , Ai-Dong Wang 1 , Yi-Ming Ji 1 , Yong-Fu Xu 1 , Ji-Cheng Li 3 , Wei-Ping Zhou 2 , Wei-Jie Zhou 4 , Hai-Xiong Han 1 1 Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai 317000, China 2 Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China 3 Institute of Cell Biology, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou 310058, China 4 Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA # Contributed equally to this work. Correspondence to: Dr. Hai-Xiong Han, e-mail: hanhaixiong@yeah.net Dr. Wei-Jie Zhou, e-mail: weijie@umich.edu Dr. Wei-Ping Zhou, e-mail: ehphwp@126.com Keywords: Hepatocellular carcinoma, liver tumorigenesis, Proliferation, Rpb3. Received: July 07, 2014      Accepted: August 23, 2014      Published: September 02, 2014 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.