Interferon-Induced Transmembrane Protein 3 Expression Upregulation Is Involved in Progression of Hepatocellular Carcinoma.

Yuli Hou,Mengdan Gao,Ang Li,Yan Zhao,Jinli Lou,Ling Qin,Fudong Lv,Yonghong Zhang,Jing Chang,Jianping Sun,Shanshan Wang,Udayan Apte

doi:10.1155/2021/5612138

Abstract

Purpose 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. Material and Methods. 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. Results 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. Conclusion 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.

Highlights

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death according to World Health Organization (WHO) data [1, 2]
The expression of Interferoninduced transmembrane protein 3 (IFITM3) was significantly higher in HCC patients than in normal controls in subgroup analysis based on gender, age, weight, tumor grade, and TP53 mutation (Figure 1(d))
In order to verify the expression level of IFITM3 protein in HCC samples and nontumor samples, we examined the expression of IFITM3 protein in 14 pairs of hepatic tissues compared with adjacent normal hepatic tissues

Summary

Introduction

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death according to World Health Organization (WHO) data [1, 2]. The occurrence and development of HCC are the result of all kinds of factors, among which genes and their polymorphisms play an important role in the susceptibility and progression of hepatic cancer [3]. Increasing studies have reported that IFITM3 is abnormally expressed in various types of human cancers [8,9,10] and that it participates in tumor development. The epithelial-mesenchymal transition (EMT) is likely to be BioMed Research International induced by the regulation of signaling pathways through oncogenes leading to tumor progression and metastasis [14]. The expression of vimentin which is upregulated in EMT is an EMT marker [15]

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