Knockdown of CCT2 inhibits the malignant progression of hepatocellular carcinoma cells by impairing STAT3 activation.

Hepatocellular carcinoma (HCC) is an aggressive liver malignancy, the molecular mechanisms underlying the progression of which are not fully understood. As a component of the chaperonin‑containing tailless complex polypeptide 1 (TCP1) ring complex, chaperonin‑containing TCP1 subunit 2 (CCT2) participates in the development of numerous types of liver disease. However, the potential role of CCT2 in regulating HCC malignant behaviors remains unclear. In the present study, bioinformatics analysis of patients with HCC from public datasets (The Cancer Genome Atlas‑Liver HCC, International Cancer Genome Consortium‑Liver Cancer‑Riken‑Japan and OEP00000321) demonstrated that CCT2 expression was upregulated in HCC tissue. High expression of CCT2 was also associated with an unfavorable overall survival prognosis. CCT2 knockdown was shown to inhibit the proliferation, migration, invasion and stemness and promote the apoptosis of HCC cells in vitro, as evidenced by EdU, colony formation, flow cytometry, caspase‑3/7 activity, gap closure, Transwell and tumor‑sphere formation assays. Consistently, knocking down CCT2 also suppressed the subcutaneous tumor proliferation and hematogenous lung metastasis of the human HCC HCCLM3 cells in vivo. Furthermore, downregulation of CCT2 decreased the phosphorylation of STAT3, as well as the expression of myeloid cell leukemia sequence 1, matrix metalloproteinase 2 and SRY‑box transcription factor 2 in vitro and in vivo. However, IL‑6 treatment rescued the levels of phosphorylated STAT3 and counteracted the inhibitory effects of CCT2 knockdown on proliferation and invasion. The findings suggest that CCT2 promotes HCC by activating the STAT3 signaling pathway. Therefore, CCT2 may serve as a survival biomarker and precision treatment target in HCC.