Tan Yiao, Zhao Fangfang, Liu Shuhan, Huang Tao, Zang Chunbao, Sha Dan, Kong Lingsuo, Ge Fangfang, Huang Dabing, Pu Youguang
Department of Urology Surgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, Anhui, China.
Department of Cancer Epigenetics Program, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, Anhui, China.
Bladder Cancer. 2022 Jun 3;8(2):165-177. doi: 10.3233/BLC-211623. eCollection 2022.
Bladder cancer is the second most common urological cancer worldwide, with low early diagnosis and high mortality. The limited progress in diagnostics and treatment greatly impedes the survival of bladder cancer patients.
Potential therapeutic biomarkers are urgently needed for future clinical treatment.
We analyzed the sequencing data and corresponding clinicopathological features and survival information of bladder cancer patients in the TCGA database and identified a new zinc finger protein 485 gene, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients and was verified in cells, animal models and tissue microarrays.
We found that inhibition of ZNF485 in the bladder cancer cell lines T24 and 5637 obviously inhibited proliferation and promoted the apoptosis of cancer cells. Furthermore, wound healing and invasion assays showed that downregulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-shRNA transfection obviously inhibited tumor growth in nude mice. Immunohistochemical results of clinical samples showed that the expression level of ZNF485 protein in cancer tissues was higher than that in adjacent tissues. Mechanistic analysis identified possible downstream target genes.
Taken together, the results provide evidence that ZNF485 is involved in bladder cancer proliferation and might be a potential therapeutic biomarker for the treatment of this disease.
膀胱癌是全球第二常见的泌尿系统癌症，早期诊断率低且死亡率高。诊断和治疗方面的有限进展极大地阻碍了膀胱癌患者的生存。
未来临床治疗迫切需要潜在的治疗生物标志物。
我们分析了TCGA数据库中膀胱癌患者的测序数据以及相应的临床病理特征和生存信息，鉴定出一种新的锌指蛋白485基因，命名为ZNF485，其在膀胱癌患者组织中高表达，并在细胞、动物模型和组织芯片中得到验证。
我们发现，在膀胱癌细胞系T24和5637中抑制ZNF485可明显抑制癌细胞增殖并促进其凋亡。此外，伤口愈合和侵袭实验表明，ZNF485的下调显著降低了T24和5637细胞的迁移和侵袭能力。另外，ZNF485-shRNA转染明显抑制了裸鼠体内肿瘤的生长。临床样本的免疫组化结果显示，癌组织中ZNF485蛋白的表达水平高于癌旁组织。机制分析确定了可能的下游靶基因。
综上所述，这些结果提供了证据表明ZNF485参与膀胱癌增殖，可能是治疗该疾病的潜在治疗生物标志物。
