Zhou Baoyong, Yang Changhong, Yan Xiong, Shi Zhengrong, Xiao Heng, Wei Xufu, Jiang Ning, Wu Zhongjun
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Bioinformatics, Chongqing Medical University, Chongqing, China.
Front Oncol. 2021 Jan 21;10:606790. doi: 10.3389/fonc.2020.606790. eCollection 2020.
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is an inner mitochondrial membrane protein that has been reported to be involved in many primary tumors and may regulate many biological processes. However, the biological role and molecular mechanism of LETM1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that LETM1 was highly expressed in HCC tissues and cell lines and that higher LETM1 expression was associated with a lower overall survival rate in HCC patients. In addition, knockdown of LETM1 inhibited proliferation and enhanced apoptosis and autophagy in the Huh 7 and QGY-7701 liver cancer cell lines. Mechanistically, knockdown of LETM1 dissociated the Beclin-1/Bcl-2 complex through phosphorylation of AMPK and Bcl-2. These results demonstrated that LETM1 is involved in the development of HCC and could be a novel therapeutic target in HCC.
含亮氨酸拉链/EF手结构域的跨膜蛋白1（LETM1）是一种线粒体内膜蛋白，据报道它参与多种原发性肿瘤，可能调控多种生物学过程。然而，LETM1在肝细胞癌（HCC）进展中的生物学作用和分子机制仍 largely未知。在本研究中，我们发现LETM1在HCC组织和细胞系中高表达，且LETM1表达水平较高与HCC患者较低的总生存率相关。此外，敲低LETM1可抑制Huh 7和QGY-7701肝癌细胞系的增殖，增强其凋亡和自噬。机制上，敲低LETM1通过使AMPK和Bcl-2磷酸化来解离Beclin-1/Bcl-2复合物。这些结果表明LETM1参与HCC的发生发展，可能是HCC的一个新的治疗靶点。
