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NKX6.1 抑制结直肠癌的肿瘤发生、转移和化疗耐药性。

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

机构信息

Graduate Institute of Medical Sciences, National Defense Medical Center, No.161, Sec.6, Minquan East Rd., Neihu District, Taipei 11490, Taiwan.

Division of Urological Surgery, Department of Surgery, Tri-Service General Hospital Songshan Branch, No.131, Jiankang Rd., Songshan District, Taipei 10581, Taiwan.

出版信息

Int J Mol Sci. 2020 Jul 19;21(14):5106. doi: 10.3390/ijms21145106.

DOI:10.3390/ijms21145106
PMID:32707737
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7404324/
Abstract

Accumulating evidence suggests that NKX6.1 (NK homeobox 1) plays a role in various types of cancer. In our previous studies, we identified 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 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.

摘要

越来越多的证据表明 NKX6.1（NK 同源盒 1）在多种类型的癌症中发挥作用。在我们之前的研究中，我们确定了异常甲基化是一个很有前途的标志物，并证明 NKX6.1 基因通过表观遗传调控宫颈癌中的上皮间质转化（EMT）发挥转移抑制作用。最近，我们已经证明了甲基化与结直肠癌（CRC）的化疗反应有关。然而，NKX6.1 在 CRC 肿瘤发生中的生物学功能仍不清楚。在这项研究中，我们表明 NKX6.1 在体外和体内均抑制肿瘤发生和转移能力。NKX6.1 通过调节 EMT 部分抑制细胞侵袭。NKX6.1 的过表达增强了 CRC 细胞的化疗敏感性。为了进一步探索 NKX6.1 如何发挥其肿瘤抑制功能，我们使用 RNA 测序技术进行了全面分析。结果表明，差异表达基因（DEGs）主要与细胞迁移、药物反应、转录因子活性和生长因子活性有关，这表明这些 DEGs 参与了 NKX6.1 抑制癌症侵袭和转移的功能。我们的结果表明，NKX6.1 作为肿瘤抑制因子的部分功能是通过抑制 EMT 和增强 CRC 的化疗敏感性来实现的，使其成为一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e01f/7404324/b9ef2bd48b1f/ijms-21-05106-g008a.jpg
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