TXNDC9 knockdown inhibits lung adenocarcinoma progression by targeting YWHAG

Abstract

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 (TXNDC 9) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein γ (YWHAG; also known as 14-3-3γ) in the progression of LUAD . The expression of TXNDC 9 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 TXNDC 9 mRNA and protein expression levels, respectively, in in vitro studies. To investigate the role of TXNDC 9 in the progression of LUAD , TXNDC 9 was silenced using small interfering RNA transfection. Furthermore, the viability, proliferation, migration, invasiveness and apoptosis of TXNDC 9-silenced A549 cells were detected using Cell Counting Kit (CC K)-8, colony formation, wound healing, Transwell and TUNEL assays, respectively. The association between TXNDC 9 and YWHAG was analyzed using STRIN G 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. TXNDC 9 expression was markedly upregulated in lung cancer cells, particularly A549 cells, and silencing of TXNDC 9 expression suppressed the viability of the lung cancer cells. The results also revealed that TXNDC 9 silencing exerted inhibitory effects on the viability, proliferation, migration and invasiveness of A549 cells, whereas the apoptotic rate was increased. Similar to TXNDC 9, YWHAG expression was also upregulated in the A549 cells. Furthermore, TXNDC 9 was demonstrated to bind to YWHAG and was positively associated with YWHAG. YWHAG overexpression reversed the inhibitory effects of TXNDC 9 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 TXNDC 9 exerted suppressive effects on LUAD , whereas YWHAG overexpression reversed the inhibitory effects of TXNDC 9 silencing on LUAD . Therefore, TXNDC 9 silencing may exert protective effects against LUAD by targeting YWHAG.