CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR-425.
CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR-425.
复制标题
CTNNA3 是肝细胞癌中的肿瘤抑制因子，并被 miR-425 抑制
DOI：
10.18632/oncotarget.6978
复制
发表时间：
2016-02-16
期刊：
影响因子：
--
通讯作者：
Zhang HQ
中科院分区：
文献类型：
--
作者：
He B;Li T;Guan L;Liu FE;Chen XM;Zhao J;Lin S;Liu ZZ;Zhang HQ
肝细胞癌（HCC）是世界范围内常见的主要死亡原因。在这里，我们确定了细胞-细胞粘附基因CTNNA 3是HCC中的肿瘤抑制基因。CTNNA 3可抑制肝癌细胞的增殖、迁移和侵袭。在这些细胞中，CTNNA 3抑制Akt信号，并反过来降低增殖细胞核抗原（PCNA）和基质金属肽酶MMP-9，并增加细胞周期抑制因子p21 Cip 1/Waf 1。同时，CTNNA 3在HCC中被miR-425抑制。miR-425直接与CTNNA 3的3′UTR结合并抑制其表达。CTNNA 3的抑癌功能和miR-425的致癌功能在裸鼠肝癌细胞移植瘤中得到进一步证实。miR-425/CTNNA 3轴可能为肝癌的发病机制提供新的线索，并为肝癌的治疗提供新的思路。
Hepatocellular carcinoma (HCC) is a common and leading cause of death worldwide. Here, we identified that a cell-cell adhesion gene, CTNNA3, is a tumor suppressor in HCC. CTNNA3 inhibited the proliferation, migration and invasion of HCC cell lines. In these cells, CTNNA3 inhibited Akt signal, and in turn decreased the proliferating cell nuclear antigen (PCNA) and the matrix metallopeptidase MMP-9, and increased the cell cycle inhibitor p21Cip1/Waf1. Meanwhile, CTNNA3 is inhibited by miR-425 in HCC. The miR-425 directly bound to the 3′UTR of CTNNA3 and inhibited its expression. The tumor suppressor function of CTNNA3 and the oncogenic function of miR-425 were further confirmed in HCC cell xenograft in nude mice. The miR-425/CTNNA3 axis may provide insights into the mechanisms underlying HCC, and contribute to potential therapeutic strategy of HCC.