Chen Qianhui, Lu Xinyu, Xie Jiayi, Ma Na, Xu Weikang, Zhang Zhiming, Huang Xuan, Liu Hongyan, Hou Jinlin, Zhang Xiaoyong, Zhu Wei
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Pathology, The First People's Hospital of Foshan, Foshan, China.
Front Oncol. 2022 Mar 31;12:813275. doi: 10.3389/fonc.2022.813275. eCollection 2022.
Hepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. L antigen family member 3 (LAGE3) is a prognostic biomarker and associated with progression in a variety of tumors. However, little has been reported about the role and potential mechanism of LAGE3 in HCC.
The clinical value and function of LAGE3 in HCC were obtained from multiple online databases. The potential functions and pathways of LAGE3 in HCC were analysed by R package of "clusterProfiler". LAGE3 knockdown cells were constructed in HepG2, HuH7 and MHCC97H cell lines, respectively. The biological roles of LAGE3 were examined by and experiments.
LAGE3 was upregulated in HCC tissues compared with normal tissues, and high expression of LAGE3 was significantly associated with several clinical characteristics and indicated a worse prognosis of HCC. The co-expressed genes of LAGE3 could be enriched in the mTOR signaling pathway in HCC. LAGE3 was upregulated in HCC cell lines. Functionally, knocking down LAGE3 expression not only increased apoptosis and inhibited growth rate, cell death mediated by T cells, colony formation, migration and invasion ability of HCC cell lines , but also reduced the progression of HCC in the subcutaneous xenotransplanted tumor model.
Our results suggested that LAGE3 served as an oncogenic factor of HCC and could be a potential biomarker and therapeutic target for HCC.
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。L抗原家族成员3（LAGE3）是一种预后生物标志物，与多种肿瘤的进展相关。然而，关于LAGE3在HCC中的作用和潜在机制的报道较少。
从多个在线数据库中获取LAGE3在HCC中的临床价值和功能。通过“clusterProfiler”的R包分析LAGE3在HCC中的潜在功能和途径。分别在HepG2、HuH7和MHCC97H细胞系中构建LAGE3敲低细胞。通过 和 实验检测LAGE3的生物学作用。
与正常组织相比，LAGE3在HCC组织中上调，LAGE3的高表达与多种临床特征显著相关，提示HCC预后较差。LAGE3的共表达基因可富集于HCC的mTOR信号通路中。LAGE3在HCC细胞系中上调。在功能上，敲低LAGE3表达不仅增加了HCC细胞系的凋亡、抑制了生长速率、T细胞介导的细胞死亡、集落形成、迁移和侵袭能力，还降低了皮下异种移植瘤模型中HCC的进展。
我们的结果表明，LAGE3是HCC的致癌因子，可能是HCC的潜在生物标志物和治疗靶点。
