Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
J Cell Biochem. 2019 Apr;120(4):5449-5458. doi: 10.1002/jcb.27824. Epub 2018 Oct 25.
Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy and the second leading cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) is an oncogene in breast cancer, while its role in HCC remains unclear. Here, we found that PSMC3IP was critical for the cell proliferation and tumorigenic capacity of HCC cells. Upregulation of PSMC3IP was observed in HCC specimens, and high PSMC3IP expression predicted poor overall survival of HCC patients. In vitro, knockdown of PSMC3IP blunted the proliferation and colony formation of BEL-7404 and SMMC-7721 cells. Likewise, PSMC3IP silencing suppressed the xenografted tumor development of BEL-7404 cells. Mechanistically, apoptosis was enhanced after PSMC3IP knockdown in both BEL-7404 and SMMC-7721 cells. At the molecular level, TP53 and GNG4 were upregulated and eukaryotic translation initiation factor 4E (EIF4E) and insulin like growth factor 1 receptor (IGF1R) were downregulated in shPSMC3IP compared with shCtrl BEL-7404 cells. Therefore, targeting PSMC3IP maybe a promising strategy for HCC.
肝细胞癌（HCC）是全球第五大常见恶性肿瘤，也是癌症相关死亡的第二大主要原因。蛋白酶体 26S 亚基 ATP 酶 3 相互作用蛋白（PSMC3IP）是乳腺癌中的致癌基因，但其在 HCC 中的作用尚不清楚。在这里，我们发现 PSMC3IP 对 HCC 细胞的增殖和致瘤能力至关重要。在 HCC 标本中观察到 PSMC3IP 上调，高 PSMC3IP 表达预示着 HCC 患者总体生存率差。在体外，PSMC3IP 的敲低削弱了 BEL-7404 和 SMMC-7721 细胞的增殖和集落形成。同样，PSMC3IP 沉默抑制了 BEL-7404 细胞的异种移植肿瘤的发展。在 BEL-7404 和 SMMC-7721 细胞中，PSMC3IP 敲低后凋亡增强。在分子水平上，与 shCtrl BEL-7404 细胞相比，shPSMC3IP 细胞中 TP53 和 GNG4 上调，真核翻译起始因子 4E（EIF4E）和胰岛素样生长因子 1 受体（IGF1R）下调。因此，靶向 PSMC3IP 可能是 HCC 的一种有前途的策略。
