Restraint of chaperonin containing T-complex protein-1 subunit 3 has antitumor roles in non-small cell lung cancer via affection of YAP1

Abstract

The implication of chaperonin containing T-complex protein-1 subunit 3 (CCT3) in carcinogenesis has been observed in a diverse malignancies. However, the relevance of CCT3 in non-small cell lung cancer (NSCLC) has not been well addressed. This research is dedicated to investigating the expression pattern and functional role of CCT3 in NSCLC. An elevation in CCT3 levels was observed in NSCLC tissue, which was linked to a reduced overall survival rate. The inhibition of CCT3 by shRNA-mediated gene silencing induced suppressive effects on the transformative phenotypes of NSCLC cells, including the inhibition of cell proliferation and invasion, and the induction of cell cycle arrest and apoptosis. Further investigation revealed that the silencing of CCT3 led to the suppression of Yes-associated protein 1 (YAP1), and decreased the expression of YAP1 target genes in NSCLC cells. The activation of YAP1 via forced expression of constitutively active YAP1 mutant reversed CCT3-restraint-evoked antitumor effects in NSCLC cells. Crucially, NSCLC cells with CCT3 silencing also exhibited weakened oncogenicity in nude mice associated with the down-regulation of YAP1 activation in xenografts. To sum up, these observations of our work show that the inhibition of CCT3 produces antitumor effects in NSCLC via the suppression of YAP1. This study unveils a possible role CCT3/YAP1 axis in NSCLC and suggests CCT3 as a candidate anticancer target.

Keywords: CCT3; Non-small cell lung cancer; YAP1.