TIFA Promotes Cell Survival and Migration in Lung Adenocarcinoma

Abstract

Background/Aims: TNF-α receptor-associated factor (TRAF)-interacting protein with a forkhead-associated (FHA) domain (TIFA) may mediate the impact of TRAF on the development of lung cancer. The current study was conducted to investigate the expression of TIFA in lung adenocarcinoma and its potential role in the regulation of cancer cell proliferation and migration, and its influence on patient survival. Methods: Specimens of lung adenocarcinoma tissues and their adjacent normal lung tissues were obtained from 116 patients who underwent surgical resection of lung cancer. The expression of TIFA in the lung tissues was examined by immunohistochemistry, immunoblotting, and real-time RT-PCR in four different lung cancer cell lines and one normal bronchial epithelial cell line (BEAS-2B). TIFA was silenced by RNAi technique, and cell proliferation was then assessed by the CCK8 method. Furthermore, cell migration was determined by wound-healing trans-well and wound-healing migration assays. Additionally, cell-cycle arrest and apoptosis were assessed by flow cytometry analysis. Results: TIFA was positively detected in 63 (54.3%) out of 116 lung adenocarcinoma specimens, which was significantly higher than the respective rate established in normal tissues adjacent to the tumor (30.1%, p < 0.05). The overall survival rate was significantly lower in the patients with positive TIFA expression than that in the patients with negative TIFA expression (p < 0.05). TIFA was also highly expressed in the lung cancer cell lines (H1299, H1975, and HCC827) tested. It is noteworthy that siRNA suppressed the expression of TIFA, which contributed to the attenuation of cell proliferation and migration, but promoted cell-cycle arrest and apoptosis. Furthermore, the silencing of TIFA caused upregulation of p53, p21, and cleaved-caspase-3, but downregulation of Bcl-2, cyclin D1, and CDK4, as well as phosphorylation of IKKß, IκB, and p65. Conclusions: TIFA may serve as a biomarker in the prediction of lung adenocarcinoma. Furthermore, TIFA may modulate lung cancer cell survival and proliferation through regulating the synthesis of apoptosis-associated proteins.

TCF19 contributes to cell proliferation of non‐small cell lung cancer by inhibiting FOXO1

“…Of note, LAC and SCC account for 50% and 30%, respectively (Larrayoz et al, ). Despite the remarkable advances in diagnosis and therapeutic technology, the 5‐year survival rate for NSCLC patients is still approximately 15% (Miller, ; Liu et al, ; Men et al, ). Therefore, better understanding of the cellular and molecular changes in lung cancer is essential.…”

Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPARα-regulated genes

“…Among these, the expression of TNF-α receptor-associated factor (TRAF)-interacting protein with a forkheadassociated (FHA) domain (TIFA) was significantly decreased in the fatp2-/-livers. High expression of this protein is associated with poor prognosis in lung adenocarcinoma (33). The expression of TIFA is also increased in acute myeloid leukemia (34).…”

TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis

“…TIFA and TIFAB have been implicated in various cellular signaling pathways associated with hematopoietic and immune cells. TIFA promotes nuclear factor κB (NF-κB) and c-Jun N-terminal kinase (JNK) signaling in splenic B cells by binding TRAF6 and promoting Toll-like receptor (TLR) signaling following inflammatory stimuli, ultimately leading to cell cycle progression and cell survival under infectious or DNA-damaging conditions ( Ea et al, 2004 ; Fu et al, 2018 ; Gall et al, 2017 ; Gaudet et al, 2017 ; Men et al, 2018 ; Takatsuna et al, 2003 ; Zimmermann et al, 2017 ). Recently, TIFA was implicated as an indispensable cytosolic innate immune sensor for a metabolic intermediate of lipopolysaccharide biosynthesis ( Gaudet et al, 2015 ).…”