Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway
Specific knockdown of HOXB7 inhibits cutaneous squamous cell carcinoma cell migration and invasion while inducing apoptosis via the Wnt/β-catenin signaling pathway
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DOI：
10.1152/ajpcell.00291.2017
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发表时间：
2018-11-01
影响因子：
5.5
通讯作者：
Chen, Hong-Quan
中科院分区：
文献类型：
--
作者：
Gao, Dong;Chen, Hong-Quan
转移性皮肤鳞状细胞癌（CSCC）是与非黑色素瘤皮肤癌相关的主要死亡原因。同源框B7（HOXB 7）参与癌症已经被报道。因此，本研究拟探讨HOXB7在CSCC中的作用及其与Wnt/beta-catenin信号通路的关系。最初，进行了CSCC的基于微阵列的基因表达谱分析，并且基于GSE 66359的微阵列数据将HOXB 7鉴定为上调基因。在此之后，实验结果表明HOXB 7和β-连环蛋白形成复合物，证明内源性HOXB 7与β-连环蛋白结合。随后，用针对HOXB 7的siRNA或Wnt/β-连环蛋白信号传导途径的抑制剂处理CSCC细胞，以分析HOXB 7对CSCC细胞的任何潜在调节机制。还观察了裸鼠中涉及异种移植物的肿瘤生长，以探索HOXB 7是否可以通过体内培养调节皮下肿瘤生长。为了研究HOXB 7对Wnt/β-catenin信号通路的潜在影响，我们测定了HOXB 7和Wnt/β-catenin信号通路下游基因的表达。值得注意的是，siRNA介导的HOXB 7敲低抑制了Wnt/β-连环蛋白信号通路的激活，从而阻碍了细胞活力、迁移和侵袭以及肿瘤生长的进展，尽管相反地促进了细胞凋亡。综上所述，HOXB 7的沉默具有使Wnt/β-catenin信号通路失活的机制，从而加速细胞凋亡并抑制CSCC中的细胞迁移和侵袭，这可能为CSCC治疗提供候选靶点。
Metastatic cutaneous squamous cell carcinoma (CSCC) is a major cause of death associated with nonmelanoma skin cancer. The involvement of homeobox B7 (HOXB7) in cancers has been reported. Thus, the current study intends to explore the effect of HOXB7 on CSCC and its relationship with the Wnt/beta-catenin signaling pathway. Initially, microarray-based gene expression profiling of CSCC was performed, and HOXB7 was identified as an upregulated gene based on the microarray data of GSE66359. Following this, the experimental results indicated that HOXB7 and beta-catenin formed a composite, demonstrating that endogenous HOXB7 binds to beta-catenin. Subsequently, CSCC cells were treated with siRNA against HOXB7 or an inhibitor of the Wnt/beta-catenin signaling pathway to analyze any underlying regulatory mechanism of HOXB7 on the CSCC cells. Tumor growth involving xenografts in nude mice was also observed so as to explore whether or not HOXB7 could regulate subcutaneous tumor growth through in vivo culturing. To investigate the potential effects of HOXB7 on the Wnt/beta-catenin signaling pathway, we determined the expression of HOXB7 and downstream genes of the Wnt/beta-catenin signaling pathway. Notably, siRNA-mediated knockdown of HOXB7 inhibited the activation of the Wnt/beta-catenin signaling pathway, thereby impeding the progression of cell viability, migration, and invasion as well as of the tumor growth, although contrarily facilitating cell apoptosis. Taken together, silencing of the HOXB7 has the mechanism of inactivating the Wnt/beta-catenin signaling pathway, thereby accelerating cell apoptosis and suppressing cell migration and invasion in CSCC, which could provide a candidate target for the CSCC treatment.