NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer

International Journal of Molecular Sciences

Chun-Te Lee¹  Hsin-Hua Chung²  Yu-Lueng Shih²  Ya-Wen Lin²  Je-Ming Hu²  Yu-Ching Chou³ 

[1] Division of Urological Surgery, Department of Surgery, Tri-Service General Hospital Songshan Branch, No.131, Jiankang Rd., Songshan District, Taipei 10581, Taiwan;Graduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, Taiwan;School of Public Health, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, Taiwan;

关键词: NK6 homeobox 1 (NKX6.1);    colorectal cancer (CRC);    tumor suppressor;    metastasis;    epithelial-to-mesenchymal transition (EMT);    chemoresistance;   

DOI  :  10.3390/ijms21145106

来源: DOAJ

【 摘 要 】

Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified NKX6.1 hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through the epigenetic regulation of the epithelial-to-mesenchymal transition (EMT) in cervical cancer. More recently, we have demonstrated that NKX6.1 methylation is related to the chemotherapy response in colorectal cancer (CRC). Nevertheless, the biological function of NKX6.1 in the tumorigenesis of CRC remains unclear. In this study, we showed that NKX6.1 suppresses tumorigenic and metastatic ability both in vitro and in vivo. NKX6.1 represses cell invasion partly through the modulation of EMT. The overexpression of NKX6.1 enhances chemosensitivity in CRC cells. To further explore how NKX6.1 exerts its tumor-suppressive function, we used RNA sequencing technology for comprehensive analysis. The results showed that differentially expressed genes (DEGs) were mainly related to cell migration, response to drug, transcription factor activity, and growth factor activity, suggesting that these DEGs are involved in the function of NKX6.1 suppressing cancer invasion and metastasis. Our results demonstrated that NKX6.1 functions as a tumor suppressor partly by repressing EMT and enhancing chemosensitivity in CRC, making it a potential therapeutic target.

【 授权许可】

Unknown