Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, China.
Department of Thoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, No. 41 Xibei Road, Ningbo 315010, China.
Int J Med Sci. 2020 Mar 12;17(6):807-814. doi: 10.7150/ijms.33992. eCollection 2020.
Family with sequence similarity 83A (FAM83A) is a newly-found over-expressed oncogene in several types of cancers and associates with poor prognosis. However, the role that FAM83A may play in the carcinogenesis of non-small cell lung cancer (NSCLC) still needs to be defined. The present study aimed to investigate the function of FAM83A in NSCLC progression and to investigate the possible mechanism. Analysis of Gene Expression Omnibus (GEO) database and rt-PCR showed up-regulated expression of FAM83A in NSCLC. GEO and the Cancer Genome Atlas (TCGA) data analysis revealed that high expression level of FAM83A in NSCLC was associated with poor prognosis. experiments showed that depleting FAM83A by siRNA/shRNA significantly inhibited cell proliferation and induced cell apoptosis. Cell motility was also retarded after silencing FAM83A, as demonstrated by Transwell assay. FAM83A depletion in A549 cells also inhibited subcutaneous tumor growth and lung metastasis . Western blotting showed that silencing FAM83A decreased the phosphorylation of ERK and PI3K/Akt/mTOR. On the other hand, overexpressing FAM83A enhanced cell proliferation and invasiveness, which was repressed by PI3K inhibitor and ERK inhibitor separately. Taken together, our study suggests that FAM83A promotes tumorigenesis of NSCLC at least partly via ERK and PI3K/Akt/mTOR pathways, making it a promising therapeutic target.
家族与序列相似性 83A（FAM83A）是几种类型癌症中发现的新过表达癌基因，与预后不良相关。然而，FAM83A 在非小细胞肺癌（NSCLC）发生中的作用仍需进一步明确。本研究旨在探讨 FAM83A 在 NSCLC 进展中的作用及其可能的机制。基因表达综合数据库（GEO）和实时定量聚合酶链反应（rt-PCR）分析显示 FAM83A 在 NSCLC 中呈高表达。GEO 和癌症基因组图谱（TCGA）数据分析显示，FAM83A 在 NSCLC 中的高表达水平与预后不良相关。实验表明，siRNA/shRNA 敲低 FAM83A 可显著抑制细胞增殖并诱导细胞凋亡。Transwell 实验表明，沉默 FAM83A 后细胞迁移能力也受到抑制。在 A549 细胞中敲低 FAM83A 还抑制了皮下肿瘤生长和肺转移。Western blot 显示，沉默 FAM83A 降低了 ERK 和 PI3K/Akt/mTOR 的磷酸化。另一方面，过表达 FAM83A 增强了细胞增殖和侵袭性，而 PI3K 抑制剂和 ERK 抑制剂分别抑制了这一作用。综上所述，我们的研究表明 FAM83A 通过 ERK 和 PI3K/Akt/mTOR 通路促进 NSCLC 的肿瘤发生，使其成为有前途的治疗靶点。
