Miao Yuanxin, Zhang Weina, Liu Su, Leng Xiangfeng, Hu Chunnan, Sun Hao
Department of Plastic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 260003, Shandong, China.
Department of Environmental Art Design, Qingdao University of Science and Technology, No. 99 Songling Road, Qingdao, 260061, Shandong, China.
Discov Oncol. 2021 Apr 26;12(1):12. doi: 10.1007/s12672-021-00408-7.
Homeobox C10 (HOXC10) has been reported to participate in various cancers. However, the involvement of HOXC10 in melanoma is still unknown. Here, we attempted to determine whether HOXC10 can affect the development of melanoma. We separated melanoma tissues and the matched tumor-adjacent normal tissues from melanoma patients, and examined HOXC10 expression in the melanoma cells and tissues. Comparing with the tumor-adjacent normal tissues, HOXC10 was up-regulated in melanoma tissues. Melanoma cells also displayed an up-regulation of HOXC10. Moreover, HOXC10 inhibition suppressed cell proliferation, clone formation and promoted apoptosis of melanoma cells. Knockdown of HOXC10 also retarded migration, invasion and epithelial-mesenchymal transition (EMT) in melanoma cells. Additionally, HOXC10 accelerated Slug expression by interacting with Slug, and activating the promoter of Slug. Slug activated the YAP/TAZ signaling pathway, which was reversed by HOXC10 silencing. The in vitro assays demonstrated that inhibition of HOXC10 significantly repressed tumor growth and lung metastasis of melanoma in mice by inhibiting Slug and YAP/TAZ signaling pathway. In conclusion, this work demonstrated that HOXC10 promoted growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway. Therefore, this study suggests that inhibition of HOXC10 has therapeutic potential in melanoma.
据报道,同源盒C10(HOXC10)参与多种癌症。然而,HOXC10在黑色素瘤中的作用仍不清楚。在此,我们试图确定HOXC10是否会影响黑色素瘤的发展。我们从黑色素瘤患者中分离出黑色素瘤组织和配对的肿瘤旁正常组织,并检测黑色素瘤细胞和组织中HOXC10的表达。与肿瘤旁正常组织相比,HOXC10在黑色素瘤组织中上调。黑色素瘤细胞中HOXC10也呈上调表达。此外,抑制HOXC10可抑制黑色素瘤细胞的增殖、克隆形成并促进其凋亡。敲低HOXC10还可抑制黑色素瘤细胞的迁移、侵袭及上皮-间质转化(EMT)。此外,HOXC10通过与Slug相互作用并激活Slug启动子来加速Slug表达。Slug激活YAP/TAZ信号通路,而HOXC10沉默可逆转这一过程。体外实验表明,抑制HOXC10可通过抑制Slug和YAP/TAZ信号通路显著抑制小鼠黑色素瘤的生长和肺转移。总之,本研究表明HOXC10通过调节Slug激活YAP/TAZ信号通路促进黑色素瘤的生长和迁移。因此,本研究提示抑制HOXC10在黑色素瘤治疗中具有潜在应用价值。