NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer
Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified <i>NKX6.1</i> hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through the epigeneti...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/14/5106 |
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| author | Hsin-Hua Chung Chun-Te Lee Je-Ming Hu Yu-Ching Chou Ya-Wen Lin Yu-Lueng Shih |
| author_facet | Hsin-Hua Chung Chun-Te Lee Je-Ming Hu Yu-Ching Chou Ya-Wen Lin Yu-Lueng Shih |
| author_sort | Hsin-Hua Chung |
| collection | DOAJ |
| description | Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified <i>NKX6.1</i> 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 <i>NKX6.1</i> 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. |
| first_indexed | 2024-03-10T18:22:04Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:22:04Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a854e93e429f40bfa2102b73862d29312023-11-20T07:16:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114510610.3390/ijms21145106NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal CancerHsin-Hua Chung0Chun-Te Lee1Je-Ming Hu2Yu-Ching Chou3Ya-Wen Lin4Yu-Lueng Shih5Graduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, TaiwanDivision of Urological Surgery, Department of Surgery, Tri-Service General Hospital Songshan Branch, No.131, Jiankang Rd., Songshan District, Taipei 10581, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, TaiwanSchool of Public Health, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, TaiwanAccumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified <i>NKX6.1</i> 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 <i>NKX6.1</i> 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.https://www.mdpi.com/1422-0067/21/14/5106NK6 homeobox 1 (NKX6.1)colorectal cancer (CRC)tumor suppressormetastasisepithelial-to-mesenchymal transition (EMT)chemoresistance |
| spellingShingle | Hsin-Hua Chung Chun-Te Lee Je-Ming Hu Yu-Ching Chou Ya-Wen Lin Yu-Lueng Shih NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer International Journal of Molecular Sciences NK6 homeobox 1 (NKX6.1) colorectal cancer (CRC) tumor suppressor metastasis epithelial-to-mesenchymal transition (EMT) chemoresistance |
| title | NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer |
| title_full | NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer |
| title_fullStr | NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer |
| title_full_unstemmed | NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer |
| title_short | NKX6.1 Represses Tumorigenesis, Metastasis, and Chemoresistance in Colorectal Cancer |
| title_sort | nkx6 1 represses tumorigenesis metastasis and chemoresistance in colorectal cancer |
| topic | NK6 homeobox 1 (NKX6.1) colorectal cancer (CRC) tumor suppressor metastasis epithelial-to-mesenchymal transition (EMT) chemoresistance |
| url | https://www.mdpi.com/1422-0067/21/14/5106 |
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