Objective: Non-small cell lung carcinoma (NSCLC) is a subtype of lung cancer with unfavorable outcome. Autophagy, a mechanism responsible for cellular component degradation, has been recorded to play either a positive or negative regulatory role in apoptosis. Tectonin Beta-Propeller Repeat Containing 1 (TECPR1) is recognized relevant to autophagy. This study aimed to investigate the molecular mechanisms through which TECPR1 regulates NSCLC cell apoptosis.
Methods: Analysis of TECPR1 expression in the subcategories of NSCLC was conducted using GEPIA. Survival analysis for NSCLC patients was performed with Kaplan-Meier's plotter. The interaction between ATG5 and TECPR1 was predicted by STRING and validated through co-immunoprecipitation. NSCLC cells were transfected with short hairpin RNA against ATG5 and/or ATG5/TECPR1 overexpression plasmids, followed by viability and apoptosis assay using CCK-8 and flow cytometry. Expressions of TECPR1, ATG5, LC3-II/LC3-I, P62, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in NSCLC cells with or without transfection were assessed by qRT-PCR and/or Western blot.
Results: TECPR1 was low-expressed in LUAD and LUSC samples as well as NSCLC cells. Higher TECPR1 expression was associated with better outcomes. TECPR1 overexpression and ATG5 overexpression both decreased viability, promoted apoptosis, upregulated Bax and LC3-II/LC3-I, and downregulated P62 and Bcl-2. TECPR1 could form a complex with ATG5 in NSCLC cells. ATG5 was upregulated by TECPR1 overexpression and could positively modulate TECPR1 expression. ATG5 knockdown induced effect oppositely to TECPR1 overexpression, and this effect reversed the TECPR1 overexpression-induced effect and vice versa.
Conclusion: TECPR1 induces NSCLC cell apoptosis via ATG5 upregulation-induced autophagy promotion.
Keywords: ATG5; TECPR1; apoptosis; autophagy; non-small cell lung carcinoma.
© 2022 by the Association of Clinical Scientists, Inc.