1. Department of Cell Biology, School of Medicine, Soochow University, Suzhou, 215123 China ; 2. Department of Tumor Biotherapy, Third Affiliated Hospital of Soochow University, Changzhou, 213003 China.
1. Department of Cell Biology, School of Medicine, Soochow University, Suzhou, 215123 China.
Int J Biol Sci. 2014 Nov 18;10(10):1181-92. doi: 10.7150/ijbs.10275. eCollection 2014.
The smallest gene HBx of Hepatitis B virus (HBV) is recognized as an important viral oncogene (V-oncogene) in the hepatocarcinogenesis. Our previous work demonstrated that RMP is a cellular oncogene (C-oncogene) required for the proliferation of hepatocellular carcinoma (HCC) cells. Here we presented the collaboration between V-oncogene HBx and C-oncogene RMP in the development of HCC. The coexpression of HBx and RMP resulted in the cooperative effect of antiapoptosis and proliferation of HCC cells. In vivo, overexpression of RMP accelerated the growth of HBx-induced xenograft tumors in nude mice and vice versa HBx promoted the growth of RMP-driven xenograft tumors. Although HBx didn't regulate the expression of RMP, HBx and RMP interact with each other and collocalized in the cytoplasm of HCC cells. HBx and RMP collaboratively inhibited the expression of apoptotic factors and promoted the expression of antiapoptotic factors. This finding suggests that HBV may induce, or at least partially contributes to the carcinogenesis of HCC, through its V-oncoprotein HBx interacting with the C-oncoprotein RMP.
乙型肝炎病毒 (HBV) 的最小基因 HBx 被认为是肝癌发生过程中的重要病毒癌基因 (V-oncogene)。我们之前的工作表明，RMP 是促进肝癌细胞增殖所必需的细胞癌基因 (C-oncogene)。在这里，我们展示了 V-oncogene HBx 和 C-oncogene RMP 在 HCC 发展中的协同作用。HBx 和 RMP 的共表达导致 HCC 细胞的抗凋亡和增殖协同作用。在体内，RMP 的过表达加速了 HBx 诱导的裸鼠异种移植瘤的生长，反之亦然，HBx 促进了 RMP 驱动的异种移植瘤的生长。尽管 HBx 不调节 RMP 的表达，但 HBx 和 RMP 相互作用并在 HCC 细胞的细胞质中共定位。HBx 和 RMP 协同抑制凋亡因子的表达，促进抗凋亡因子的表达。这一发现表明，HBV 可能通过其与 C-oncoprotein RMP 相互作用的 V-oncoprotein HBx 诱导，或至少部分促进 HCC 的发生。
