ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression.

ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression.
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miR-144-3p 靶向基因 ZBTB7A 通过下调 HIC1 表达加速膀胱癌进展

DOI:
10.1186/s12935-022-02596-w
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发表时间:
2022-05-02
影响因子:
5.8
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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ZBTB 7A是POK家族转录因子中的一员,根据癌症的类型和遗传背景,ZBTB 7A在不同的癌症中发挥致癌或肿瘤抑制作用。然而,ZBTB 7A在膀胱癌(BC)中的功能和分子机制仍不清楚。通过集落形成、transwell和肿瘤形成试验检测ZBTB 7A在膀胱癌中的作用。通过qRT-PCR和Western blot分析ZBTB 7A、ZBTB 1和miR-144- 3 p的表达水平。利用生物信息学分析和双荧光素酶报告基因分析来评估ZBTB 7A对p53 1启动子活性的影响。本研究表明,ZBTB 7A的敲除抑制了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。ZBTB 7A的缺失抑制了体内肿瘤生长,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,ZBTB 7A结合到癌细胞中的高甲基化1(hypermethylated in cancer 1,HM 1)启动子,下调HM 1的表达,加速BC的恶性行为。ZBTB 7A在BC组织中的表达增加与ZBTB 1的表达呈负相关。此外,ZBTB 7A是miR-144- 3 p的靶点,其降低了BC中ZBTB 7A的表达。我们的数据表明,ZBTB 7A,miR-144- 3 p的靶向基因,通过下调BCR 1表达促进BC的肿瘤发生。在线版本包含补充材料,可通过10.1186/s12935-022-02596-w获得。
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. 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. 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. Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression. The online version contains supplementary material available at 10.1186/s12935-022-02596-w.
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