HOXD9 promote epithelial‐mesenchymal transition and metastasis in colorectal carcinoma. (12th April 2020)

• Record Type: Journal Article
• Authors: Liu, Mengwei; Xiao, Yizhi; Tang, Weimei; Li, Jiaying; Hong, Linjie; Dai, Weiyu; Zhang, Wenjing; Peng, Ying; Wu, Xiaosheng; Wang, Jing; Chen, Yaying; Bai, Yang; Lin, Jianjiao; Yang, Qiong; Wang, Yusi; Lin, Zhizhao; Liu, Side; Xiong, Jing; Wang, Jide; Xiang, Li
• Is Part Of: Cancer medicine. Volume 9:Number 11(2020)
• Page Start: 3932
• Page End: 3943
• Publication Date: 2020-04-12
• Subjects: colorectal cancer -- epithelial‐mesenchymal transition -- HOXD9 -- metastasis -- TGF‐β1; 616.994005
• DOI: 10.1002/cam4.2967
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: HOXD9, a Hox family member, is involved in cancer growth and metastasis. But, its regulation mechanism at the molecular level particularly in colorectal cancer (CRC), is mostly unknown. Methods: The HOXD9 protein expression levels were analyzed using immunofluorescence, immunohistochemistry (IHC) assays, and western blot. The in vivo and in vitro roles of HOXD9 in CRC were determined using colony formation and EdU incorporation, CCK‐8, wound scratch and transwell invasion assay, and animal models. Results: Expression of HOXD9 was higher in CRC than in matched healthy tissues. High expression of HOXD9 has significantly associated with the American Joint Committee on Cancer (AJCC) stages, tumor differentiation, lymph node metastasis, and other serious invasions, and it had a poor prognosis. In vitro, HOXD9 encouraged proliferation, movement and EMT processes in cells of CRC. Also, TGF‐β1 promoted the expression of HOXD9 and this effect was dependent on the dose and downregulation of HOXD9 repressed TGF‐β1 ‐induced EMT. In vivo, HOXD9 promoted the invasive and metastasis of CRC cells via orthotopic implantation. Conclusions: The ectopic expression of HOXD9 promoted the invasion metastasis in cells of the colorectal tumor by induction of EMT in vitro and vivo. Abstract : HOXD9 is overexpressed in CRC and increases tumorigenicity and tumor proliferation. Also, ectopic HOXD9 expression influences EMT and tumor spread both in vivo and in vitro. Therefore, the HOXD9 gene could act as an assuring therapeutic approach for treating patients suffering from CRC.