Abstract：
BACKGROUND: Zinc finger and BTB domain-containing 7A (ZBTB7A) is a member of the POK family of transcription factors that plays an oncogenic or tumor-suppressive role in different cancers depending on the type and genetic context of cancer. However, the function and molecular mechanism of ZBTB7A in bladder cancer (BC) remain elusive.
METHODS: The role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1.
RESULTS: The present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC.
CONCLUSIONS: Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.
METHODS: The role of ZBTB7A in bladder cancer was detected by colony formation, transwell, and tumor formation assays. The expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed by qRT-PCR and Western blot. Bioinformatics analysis and a dual-luciferase reporter assay were used to assess the effect of ZBTB7A on the promoter activity of HIC1.
RESULTS: The present study revealed that knockdown of ZBTB7A suppressed BC cell growth and migration, as indicated by an approximately 50% reduction in the number of colonies and an approximately 70% reduction in the number of migrated cells. Loss of ZBTB7A inhibited tumor growth in vivo, resulting in a 75% decrease in tumor volume and an 80% decrease in tumor weight. Further mechanistic studies revealed that ZBTB7A bound to the hypermethylated in cancer 1 (HIC1) promoter and downregulated HIC1 expression, accelerating the malignant behavior of BC. Increased expression of ZBTB7A in BC tissues was negatively corrected with the expression of HIC1. Moreover, ZBTB7A was a target of miR-144-3p, which decreased ZBTB7A expression in BC.
CONCLUSIONS: Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.
摘要：
背景：锌指和含BTB结构域的7A（ZBTB7A）是POK转录因子家族的成员，根据癌症的类型和遗传背景，在不同的癌症中发挥致癌或肿瘤抑制作用。然而,ZBTB7A在膀胱癌（BC）中的功能和分子机制尚不清楚。
方法：通过集落形成检测ZBTB7A在膀胱癌中的作用，transwell,和肿瘤形成测定。ZBTB7A的表达水平,通过qRT-PCR和Western印迹分析HIC1和miR-144-3p。生物信息学分析和双荧光素酶报告基因测定用于评估ZBTB7A对HIC1启动子活性的影响。
结果：本研究表明敲低ZBTB7A抑制了BC细胞的生长和迁移，如集落数量减少约50%和迁移细胞数量减少约70%所示。ZBTB7A的缺失抑制了体内肿瘤的生长，导致肿瘤体积减少75%，肿瘤重量减少80%。进一步的机制研究表明，ZBTB7A结合在高甲基化的癌症1（HIC1）启动子和下调HIC1表达，加速BC的恶性行为。BC组织中ZBTB7A的表达增加与HIC1的表达呈阴性校正。此外，ZBTB7A是miR-144-3p的靶标，降低了BC中ZBTB7A的表达。
结论：我们的数据表明ZBTB7A，miR-144-3p的靶基因，通过下调HIC1表达促进BC的肿瘤发生。
方法：通过集落形成检测ZBTB7A在膀胱癌中的作用，transwell,和肿瘤形成测定。ZBTB7A的表达水平,通过qRT-PCR和Western印迹分析HIC1和miR-144-3p。生物信息学分析和双荧光素酶报告基因测定用于评估ZBTB7A对HIC1启动子活性的影响。
结果：本研究表明敲低ZBTB7A抑制了BC细胞的生长和迁移，如集落数量减少约50%和迁移细胞数量减少约70%所示。ZBTB7A的缺失抑制了体内肿瘤的生长，导致肿瘤体积减少75%，肿瘤重量减少80%。进一步的机制研究表明，ZBTB7A结合在高甲基化的癌症1（HIC1）启动子和下调HIC1表达，加速BC的恶性行为。BC组织中ZBTB7A的表达增加与HIC1的表达呈阴性校正。此外，ZBTB7A是miR-144-3p的靶标，降低了BC中ZBTB7A的表达。
结论：我们的数据表明ZBTB7A，miR-144-3p的靶基因，通过下调HIC1表达促进BC的肿瘤发生。
