TXNDC9 knockdown inhibits lung adenocarcinoma progression by targeting YWHAG

Lung adenocarcinoma (LUAD) is the most common form of lung cancer and with the highest mortality rate. Therefore, the identification and development of effective methods for the treatment of LUAD is of great importance. The present study aimed to investigate the role of thioredoxin domain-containing protein 9 (TXNDC9) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG; also known as 14-3-3 gamma) in the progression of LUAD. The expression of TXNDC9 and its association with the survival of patients with LUAD was analyzed using Encyclopedia of RNA Interactomes. Reverse transcription-quantitative PCR and western blot analysis were used to detect TXNDC9 mRNA and protein expression levels, respectively, in in vitro studies. To investigate the role of TXNDC9 in the progression of LUAD, TXNDC9 was silenced using small interfering RNA transfection. Furthermore, the viability, proliferation, migration, invasiveness and apoptosis of TXNDC9-silenced A549 cells were detected using Cell Counting Kit (CCK)-8, colony formation, wound healing, Transwell and TUNEL assays, respectively. The association between TXNDC9 and YWHAG was analyzed using STRING and Gene Expression Profiling Interactive Analysis databases, as well as co-immunoprecipitation assays. Subsequently, YWHAG was overexpressed to similarly determine effects of YWHAG on viability, proliferation, migration, invasiveness and apoptosis of A549 cells. TXNDC9 expression was markedly upregulated in lung cancer cells, particularly A549 cells, and silencing of TXNDC9 expression suppressed the viability of the lung cancer cells. The results also revealed that TXNDC9 silencing exerted inhibitory effects on the viability, proliferation, migration and invasiveness of A549 cells, whereas the apoptotic rate was increased. Similar to TXNDC9, YWHAG expression was also upregulated in the A549 cells. Furthermore, TXNDC9 was demonstrated to bind to YWHAG and was positively associated with YWHAG. YWHAG overexpression reversed the inhibitory effects of TXNDC9 silencing on LUAD, as evidenced by increased viability, proliferation, migration and invasiveness, and decreased apoptosis, of A549 cells. The present study demonstrated that the knockdown of TXNDC9 exerted suppressive effects on LUAD, whereas YWHAG overexpression reversed the inhibitory effects of TXNDC9 silencing on LUAD. Therefore, TXNDC9 silencing may exert protective effects against LUAD by targeting YWHAG.