目的:肝细胞癌(HCC)由于其侵袭性和高死亡率而面临重大挑战。了解新的治疗靶点的作用至关重要。尽管与几种疾病有关,具有序列相似性的家族114成员A1(FAM114A1)在HCC中的作用尚不清楚.
方法:利用UALCAN和GEPIA数据库,FAM114A1在肝癌组织中的表达,同时探讨其与AKT1的相关性。通过qRT-PCR实验评估HCC细胞中的FAM114A1表达。慢病毒转导后抑制FAM114A1在这些细胞中的表达,随后的分析涉及MTT测定,划痕试验,Transwell分析,和流式细胞术研究FAM114A1耗竭对细胞增殖的影响,迁移,凋亡,和细胞周期动力学。此外,蛋白质印迹分析评估了EMT相关蛋白(Snail,MMP2、MMP9)和AKT1表达。在HCC细胞中进行AKT1的过表达,使用MTT分析和Transwell分析评估其对细胞增殖和迁移的影响。
结果:在HCC组织和细胞中观察到FAM114A1表达升高。FAM114A1抑制通过调节AKT1降低细胞增殖和迁移。FAM114A1敲低促进细胞凋亡,阻止了细胞周期,并抑制EMT。
结论:总体而言,我们的研究表明FAM114A1在肝癌细胞增殖和迁移中起作用,涉及AKT1表达的调节。此外,FAM114A1影响细胞凋亡,细胞周期,和EMT,有助于HCC的发展。这些发现强调FAM114A1是HCC治疗的潜在新治疗靶标。
OBJECTIVE: Hepatocellular carcinoma (HCC) poses a significant challenge owing to its aggressive nature and elevated mortality rates. Understanding the role of novel therapeutic targets is essential. Although linked to several diseases, the role of the family with sequence similarity 114 member A1 (FAM114A1) in HCC remains unclear.
METHODS: Utilizing UALCAN and GEPIA databases, the expression of FAM114A1 in HCC tissues was examined, alongside exploring its correlation with
AKT1. FAM114A1 expression in HCC cells was assessed through qRT-PCR experiments. Following lentiviral transduction to suppress FAM114A1 expression in these cells, subsequent analyses involved MTT assays, scratch assays, Transwell analysis, and flow cytometry to investigate the impact of FAM114A1 depletion on cell proliferation, migration, apoptosis, and cell cycle dynamics. Furthermore, Western blot analysis assessed EMT-related proteins (Snail, MMP2, MMP9) and
AKT1 expression. Overexpression of
AKT1 in HCC cells was performed, and its effects on cell proliferation and migration were assessed using MTT assays and Transwell analysis.
RESULTS: Elevated FAM114A1 expression was observed in HCC tissues and cells. FAM114A1 suppression reduced cell proliferation and migration by modulating
AKT1. FAM114A1 knockdown promoted apoptosis, arrested the cell cycle, and inhibited EMT.
CONCLUSIONS: Overall, our study suggests that FAM114A1 plays a role in HCC cell proliferation and migration, involving the modulation of
AKT1 expression. Furthermore, FAM114A1 impacts apoptosis, cell cycle, and EMT, contributing to HCC development. These findings highlight FAM114A1 as a potential novel therapeutic target for HCC treatment.