Zheng Yong-Jun, Li Wen-Min, Zheng Li-Chuan, Zhou Yan-Feng, Wang Jian, Xia Wei-Mu, Ye Wei-Jing, Yu Jia-Shun
Department of Urology, Punan Hospital of Shanghai Pudong New Area, Shanghai 200125, China.
Department of Urology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.
Zhonghua Nan Ke Xue. 2024 Jul;30(7):579-587.
To study the expression of the Homeobox C6 (HOXC6) gene in the homeobox family in PCa, its effect on the biological behavior of PCa cells and its action mechanism.
Based on the studies of HOXC6 retrieved from the database of Gene Expression Profiling Interactive Analysis (GEPIA), we analyzed the expression of HOXC6 in PCa and the relationship of its expression level with the survival prognosis of the patients. We detected the expression of the HOXC6 protein in PCa tissues and cells by Western blot, stably interfered with the expression of the HOXC6 gene in human PCa DU145 and PC-3 cells and normal prostatic epithelial RWPE-1 cells using the siRNA plasmid, and determined the effects of HOXC6 on the proliferation, migration and invasiveness of PCa cells by CCK8, plate cloning and scratch healing and Transwell invasion assays. Using the GEPIA database, we analyzed the correlation of the Wnt tumor inhibitory factor-secreted frizzled-related protein 1 (SFRP1) gene with HOXC6, and detected the expressions of HOXC6, SFRP1, Wnt and β-catenin in PC-3 cells after siRNA-HOXC6 transfection by Western blot.
The expression of HOXC6 was dramatically higher in the PCa than in the normal prostate tissue (P< 0.01), and in the PCa cells than in the normal prostatic epithelial cells (P< 0.01). Bioinformatics analysis indicated a lower survival rate of the PCa patients with a high than those with a low HOXC6 expression (P = 0.011). The relative expression of the HOXC6 protein, absorbance value, number of clones formed and number of invaded cells were significantly lower in the siRNA group than in the negative controls (P< 0.05). According to the GEPIA database, highly expressed SFRP1 was associated with a good prognosis of PCa, and the protein expressions of Wnt and β-catenin were markedly increased while that of SFRP1 decreased in the PCa PC-3 cell line (P< 0.05). The expressions of the Wnt and β-catenin proteins were decreased and that of SFRP1 increased significantly in the siRNA-HOXC6 transfection group compared with those in the siRNA negative control and PCa PC-3 groups (P< 0.05).
HOXC6 is highly expressed in PCa tissues and related to the proliferation, migration and invasiveness of PCa cells. HOXC6 promotes the growth of DU145 and PC-3 cells in PCa by inhibiting the SFRP1/Wnt/β-catenin signaling pathway, and may be a potential target for clinical treatment of PCa.
研究同源盒C6（HOXC6）基因在前列腺癌（PCa）同源盒家族中的表达情况、其对PCa细胞生物学行为的影响及其作用机制。
基于从基因表达谱交互式分析（GEPIA）数据库检索到的HOXC6相关研究，分析HOXC6在PCa中的表达及其表达水平与患者生存预后的关系。通过蛋白质免疫印迹法检测PCa组织和细胞中HOXC6蛋白的表达，利用小干扰RNA（siRNA）质粒稳定干扰人PCa DU145和PC-3细胞以及正常前列腺上皮RWPE-1细胞中HOXC6基因的表达，并通过细胞计数试剂盒-8（CCK8）法、平板克隆法、划痕愈合实验和Transwell侵袭实验确定HOXC6对PCa细胞增殖、迁移和侵袭能力的影响。利用GEPIA数据库分析Wnt肿瘤抑制因子分泌型卷曲相关蛋白1（SFRP1）基因与HOXC6的相关性，并通过蛋白质免疫印迹法检测siRNA-HOXC6转染后PC-3细胞中HOXC6、SFRP1、Wnt和β-连环蛋白的表达。
HOXC6在PCa中的表达显著高于正常前列腺组织（P<0.01），在PCa细胞中的表达显著高于正常前列腺上皮细胞（P<0.01）。生物信息学分析表明，HOXC6高表达的PCa患者生存率低于低表达患者（P = 0.011）。siRNA组中HOXC6蛋白的相对表达量、吸光度值、形成的克隆数和侵袭细胞数均显著低于阴性对照组（P<0.05）。根据GEPIA数据库，SFRP1高表达与PCa的良好预后相关，在PCa的PC-3细胞系中，Wnt和β-连环蛋白的蛋白表达显著增加，而SFRP1的表达降低（P<0.05）。与siRNA阴性对照组和PCa的PC-3组相比，siRNA-HOXC6转染组中Wnt和β-连环蛋白的蛋白表达降低，SFRP1的表达显著增加（P<0.05）。
HOXC6在PCa组织中高表达，与PCa细胞的增殖、迁移和侵袭能力相关。HOXC6通过抑制SFRP1/Wnt/β-连环蛋白信号通路促进PCa中DU145和PC-3细胞的生长，可能是PCa临床治疗的潜在靶点。
