TSC22D2 Regulates ACOT8 to Delay the Malignant Progression of Colorectal Cancer

Abstract

Nana Zhou,1,* Chaoqin Guo,1,* Jingyang Du,1 Xu Zhang,1 Qiuran Xu,2 Xiaoliang Zheng,3 Linglan Tu3 1School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 310053, People’s Republic of China; 2The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 3School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linglan Tu; Xiaoliang Zheng, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: Colorectal cancer (CRC) is one of the cancers with high incidence and mortality rates worldwide. In China, there are approximately 400,000 new CRC cases each year, seriously endangering people’s life and health. Transforming growth factor β-stimulated clone 22 domain family, member 2 (TSC22D2) is widely expression in cancers, but the role of TSC22D2 in CRC are still unknown.Methods: Real‑time quantitative PCR (qRT-PCR) and Western blot were applied to determine the TSC22D2 levels. CCK-8, colony formation and transwell assays were used to determine the proliferation and metastasis abilities of CRC cells in vitro. In vivo metastatic potential was assessed using a subcutaneously injected mouse model and. Western-blot and immunoprecipitation experiments were used to study the mechanism of TSC22D2‑mediated metastasis.Results: We found TSC22D2 was deregulated in CRC tissues and cells and implied poor prognosis. Overexpression TSC22D2 significantly promoted CRC cells proliferation and tumorigenicity both in vitro and vivo, whereas knockdown TSC22D2 resulted in the opposite effects. Importantly using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting acyl-coenzyme A thioesterases 8 (ACOT8), TSC22D2 maintained stability of ACOT8. Overexpression of TCC22D2 in CRC cells can promote the expression of ACOT8 and inhibit the proliferation and metastasis of CRC cells through EMT mechanism, highlighting the possibility of TSC22D2 as a potential target in CRC development.Conclusion: In summary, the present study revealed the inhibitory effect of TSC22D2 on the proliferation of colorectal cancer cells, suggesting that TSC22D2 may be an important tumor suppressor and a potential therapeutic target during colorectal carcinogenesis.Keywords: colorectal cancer, TSC22D2, ACOT8, EMT

Keywords

• colorectal cancer
• tsc22d2
• acot8
• emt