Downregulation of FAM107A Induced by HDAC2 Boosted the Proliferation and Inhibited the Apoptosis of Lung Adenocarcinoma Cells

Abstract

Background: Non-small cell lung cancer (NSCLC) represents 85% of all lung cancer (LC) cases that are malignant tumors, while lung adenocarcinoma (LUAD) is the commonest type of NSCLC. Family with sequence similarity 107 member A (FAM107A) is a suppressor gene in many cancers, but its mechanism in LUAD has been less studied. The objective of the experiment is to explore the role and potential mechanism of FAM107A in the progression of LUAD. Methods: Expression levels of histone deacetylase 2 (HDAC2) and FAM107A in LUAD tissues/cells were determined using StarBase and quantitative reverse transcription polymerase chain reaction. In the first part, FAM107A specific short hairpin RNA (shFAM107A) was transfected into H1299 cells and FAM107A overexpression plasmid was transfected into PC9 cells. In the second part, shHDAC2 and shFAM107A were co-transfected into H1299 cells, and HDAC2 and FAM107A overexpression plasmids were co-transfected into PC9 cells. Then, chromatin immunoprecipitation assays were employed to determine HDAC2 enrichment in FAM107A promoter region. Loss- and gain-of-function experiments (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assay, and flow cytometry) were conducted to verify the regulation of FAM107A on malignant phenotype of LUAD cells. The influence of HDAC2/FAM107A axis on LUAD cell biological behaviors was verified through rescue experiments. Results: FAM107A mRNA exhibited a low expression in LUAD tissues/cells (p < 0.001). Its overexpression suppressed the viability, proliferation, and B-cell lymphoma-2 (Bcl-2) level in LUAD cells, and promoted the apoptosis as well as Bcl-2-Associated X (Bax) and Cleaved Caspase-3 protein levels (p < 0.01), while its silencing produced the opposite results. HDAC2 mRNA expression was highly expressed in LUAD tissues (p < 0.001). Its overexpression negated the aforementioned effects of FAM107A overexpression (p < 0.01), while its inhibition neutralized the effects of FAM107A silencing (p < 0.01). HDAC2 protein expression was enriched in FAM107A promoter region (p < 0.001), and FAM107A protein expression was inhibited by HDAC2 through its histone deacetylation. Conclusions: Repression of FAM107A induced by HDAC2 promotes colony formation, while inhibiting the apoptosis of LUAD cells.