TRMT6 通过 PI3K/AKT 信号通路促进肝癌进展。
TRMT6 promotes hepatocellular carcinoma progression through the PI3K/AKT signaling pathway.
机构信息
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, People's Republic of China.
Department of Gastroenterology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People's Republic of China.
出版信息
Eur J Med Res. 2023 Jan 27;28(1):48. doi: 10.1186/s40001-022-00951-1.
BACKGROUND
Hepatocellular carcinoma is one of the most common and deadly cancers. The aim of this study was to elucidate the role of tRNA methyltransferase 6 (TRMT6) during HCC progression.
METHODS
The role of TRMT6 in the progression and prognosis of HCC was confirmed by analysis of online databases and clinical human samples. The effects of up-regulation or down-regulation of TRMT6 on HCC cell proliferation and PI3K/AKT pathway-related protein expressions were verified. The molecular mechanism was investigated in vivo by constructing subcutaneous xenograft tumor model.
RESULTS
TRMT6 was overexpressed in HCC tissues and associated with Tumour-Node-Metastasis (TNM) stage, primary tumor (T) and regional lymph node (N) classification. TRMT6 expressions in HCC cell lines were higher than that in normal liver cell. TRMT6 overexpression can promote HCC cell proliferation, increase the number of S phase cells. Interference with TRMT6 reduced the PI3K/AKT pathway-related protein expressions, and was reversed by the addition of IGF1. Interference with TRMT6 inhibited tumor growth in vivo and was related to PI3K/AKT pathway.
CONCLUSIONS
Overexpression of TRMT6 promote HCC cell proliferation in vivo and in vitro through PI3K/AKT/mTOR axis, which provides a potential choice for the treatment of HCC in clinical practice.
背景
肝细胞癌是最常见和最致命的癌症之一。本研究旨在阐明 tRNA 甲基转移酶 6（TRMT6）在 HCC 进展过程中的作用。
方法
通过分析在线数据库和临床人类样本，证实了 TRMT6 在 HCC 进展和预后中的作用。验证了上调或下调 TRMT6 对 HCC 细胞增殖和 PI3K/AKT 通路相关蛋白表达的影响。通过构建皮下移植瘤模型，在体内研究了其分子机制。
结果
TRMT6 在 HCC 组织中过度表达，与肿瘤-淋巴结-转移（TNM）分期、原发肿瘤（T）和区域淋巴结（N）分类有关。HCC 细胞系中的 TRMT6 表达高于正常肝细胞。TRMT6 过表达可促进 HCC 细胞增殖，增加 S 期细胞数量。干扰 TRMT6 降低了 PI3K/AKT 通路相关蛋白的表达，而 IGF1 的加入则逆转了这一作用。干扰 TRMT6 抑制了体内肿瘤的生长，与 PI3K/AKT 通路有关。
结论
TRMT6 的过表达通过 PI3K/AKT/mTOR 轴促进 HCC 细胞在体内和体外的增殖，为临床实践中 HCC 的治疗提供了潜在的选择。
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