CCT2 Regulates ZEB1-Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma.

Abstract

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid, and its invasiveness and metastatic ability are closely related to patient prognosis. Chaperonin containing TCP1 subunit 2 (CCT2) is an important component of the molecular chaperone protein complex and has been shown to regulate cell proliferation and migration in various tumors. Epithelial-mesenchymal transition (EMT) is a critical process in tumor metastasis, and Zinc Finger E-Box Binding Homeobox 1 (ZEB1) is a core transcription factor that regulates EMT. This study aims to explore how CCT2 induces EMT gene transcription through ZEB1, thereby promoting the metastasis and tumorigenesis of PTC.

Methods: CCT2 in PTC tissues was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. siRNA and overexpression vectors were used to silence and overexpress CCT2, respectively, and the effects on PTC cell migration, invasion, proliferation, and apoptosis were observed. Rescue experiments were used to investigate the effect of CCT2 on ZEB1 and EMT-related genes. Cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay. Silencing ZEB1 was used to verify its effect on the oncogenic activity of CCT2.

Results: CCT2 was found to be highly expressed in PTC tissues (p < 0.01). In in vitro and in vivo experiments, silencing CCT2 inhibited the migration and invasion of PTC cells and their metastasis, while overexpression of CCT2 produced the opposite effect. Additionally, CCT2 promoted PTC cell proliferation and inhibited apoptosis (p < 0.01). Mechanistic studies revealed that CCT2 upregulated ZEB1 expression (p < 0.01), thereby inducing EMT gene transcription (p < 0.01). Silencing ZEB1 reduced the oncogenic effect of CCT2.

Conclusion: This study first revealed the high expression of CCT2 in PTC and its essential role in the migration, invasion, proliferation, and anti-apoptosis of tumor cells. CCT2 promotes the metastasis and tumorigenesis of PTC by regulating ZEB1 and EMT-related genes. These findings provide new potential targets for molecular targeted therapy of PTC and explore new directions for future clinical treatment strategies.