2. Academic Validation
  3. Chaperonin-containing tailless complex polypeptide 1 subunit 6A negatively regulates autophagy and protects colorectal cancer cells from cisplatin-induced cytotoxicity

Chaperonin-containing tailless complex polypeptide 1 subunit 6A negatively regulates autophagy and protects colorectal cancer cells from cisplatin-induced cytotoxicity

  • World J Gastroenterol. 2025 May 14;31(18):105729. doi: 10.3748/wjg.v31.i18.105729.
Jian-Xing Ma 1,  Xiao-Jun Li 2,  Ya-Long Li 2,  Ming-Chan Liu 1,  Rui-Hang Du 1,  Yi Cheng 1,  Liang-Jie Li 1,  Zhi-Ying Ai 1,  Jian-Tao Jiang 3,  Si-Yuan Yan 4
Affiliations

Affiliations

  • 1 Precision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining 272067, Shandong Province, China.
  • 2 Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China.
  • 3 The Second Affiliated Hospital of Xi'an Jiaotong University, Xibei Hospital, Xi'an 710000, Shaanxi Province, China.
  • 4 Precision Medicine Laboratory for Chronic Non-communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining 272067, Shandong Province, China. yansy@mail.jnmc.edu.cn.
PMID: 40496362 DOI: 10.3748/wjg.v31.i18.105729
Abstract

Background: As a member of the chaperonin-containing tailless complex polypeptide 1 (TCP1) complex, which plays a pivotal role in ensuring the accurate folding of numerous proteins, chaperonin-containing TCP1 subunit 6A (CCT6A) participates in various physiological and pathological processes. However, its effects on cell death and Cancer therapy and the underlying mechanisms need further exploration in colorectal Cancer (CRC) cells.

Aim: To explore the effects of CCT6A on cell death and Cancer therapy and the underlying mechanisms in CRC.

Methods: Cell proliferation was evaluated using the MTS assay, EdU staining, and colony growth assays. The expression of CCT6A was monitored by immunoblotting and quantitative PCR. CCT6A was knocked out by CRISPR-Cas9, and overexpressed by transfecting plasmids. Autophagy was examined by immunoblotting and the mCherry-GFP-LC3 assay. To monitor Apoptosis and Necroptosis, immunoblotting, co-immunoprecipitation, and flow cytometry were employed.

Results: Cisplatin (DDP) exerted cytotoxic effects on CRC cells while simultaneously downregulating the expression of CCT6A. Depletion of CCT6A amplified the cytotoxic effects of DDP, whereas overexpression of CCT6A attenuated these adverse effects. CCT6A suppressed Autophagy, Apoptosis, and Necroptosis under both basal and DDP-treated conditions. Autophagy inhibitors significantly enhanced the cytotoxic effects of DDP, whereas a Necroptosis inhibitor partially reversed the cell viability loss induced by DDP. Furthermore, inhibiting Autophagy enhanced both Apoptosis and Necroptosis induced by DDP.

Conclusion: CCT6A negatively modulates Autophagy, Apoptosis, and Necroptosis, and CCT6A confers resistance to DDP therapy in CRC, suggesting its potential as a therapeutic target.

Keywords

Autophagy; Chaperonin-containing tailless complex polypeptide 1 subunit 6a; Cisplatin; Colorectal cancer; Necroptosis.

Figures
Products