Department of Clinical Laboratory, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China.
Department of Clinical Laboratory, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Biomed Res Int. 2021 Mar 16;2021:5612138. doi: 10.1155/2021/5612138. eCollection 2021.
Interferon-induced transmembrane protein 3 (IFITM3) is a key signaling molecule regulating cell growth in some tumors, but its function and mechanism in hepatocellular carcinoma (HCC) remain unknown. Our study investigated the relationship between the expression of IFITM3 and HCC development. . IFITM3 expression was identified via multiple gene expression databases and investigated in HCC tissue samples. Then, PLC/PRF/5 cells were transfected with lentivirus to knock down and overexpress the expression of IFITM3. IFITM3 expression, cell proliferation, and migration were detected by qRT-PCR, western blotting, QuantiGene Plex 2.0 assay, immunohistochemistry, CCK-8, and wound healing tests. RNA-seq technology identified the PI3K/AKT/mTOR pathway as an IFITM3-related signaling pathway for investigation.
IFITM3 expression was higher in HCC tissues than in adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic potential than in those with high/medium differentiation and without metastatic potential. A higher RNA level of IFITM3 was found in samples with IFITM3 rs12252-CC genotype rather than the TT genotype. Knockdown of IFITM3 in PLC/PRF/5 cells inhibited cell proliferation and migration, blocked the expression of the PI3K/AKT/mTOR signaling pathway, and decreased the expression of vimentin. The results were opposite with the overexpression of IFITM3.
Upregulation of IFITM3 plays a role in the development of HCC. Possibly through regulating HCC cell proliferation and migration, these effects are associated with the PI3K/AKT/mTOR signaling pathway. Upregulation of IFITM3 is also associated with the IFITM3 rs12252-CC genotype.
干扰素诱导跨膜蛋白 3（IFITM3）是调节某些肿瘤细胞生长的关键信号分子，但它在肝细胞癌（HCC）中的功能和机制尚不清楚。本研究探讨了 IFITM3 表达与 HCC 发生发展的关系。
通过多个基因表达数据库鉴定 IFITM3 的表达，并在 HCC 组织样本中进行检测。然后，通过慢病毒转染 PLC/PRF/5 细胞，敲低和过表达 IFITM3 的表达。通过 qRT-PCR、western blot、QuantiGene Plex 2.0 检测、免疫组织化学、CCK-8 和划痕愈合试验检测 IFITM3 表达、细胞增殖和迁移。RNA-seq 技术鉴定出 PI3K/AKT/mTOR 通路是 IFITM3 相关的信号通路。
IFITM3 在 HCC 组织中的表达高于相邻正常组织，在低分化和转移性潜能的 HCC 组织中表达高于高/中分化且无转移性潜能的组织。IFITM3 rs12252-CC 基因型的样本中 IFITM3 的 RNA 水平较高，而 TT 基因型的样本则较低。在 PLC/PRF/5 细胞中敲低 IFITM3 抑制细胞增殖和迁移，阻断 PI3K/AKT/mTOR 信号通路的表达，并降低波形蛋白的表达。而过表达 IFITM3 则得到相反的结果。
IFITM3 的上调在 HCC 的发生发展中起作用。可能通过调节 HCC 细胞的增殖和迁移，这些作用与 PI3K/AKT/mTOR 信号通路有关。IFITM3 的上调还与 IFITM3 rs12252-CC 基因型有关。
