ZBTB7A, a miR-144-3p targeted gene, accelerates bladder cancer progression via downregulating HIC1 expression
Junqiang Liu1, Zhiyuan Chou1, Chun Li2
1Department of Urology of First Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
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.
Conclusion:
Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.
Insights
Zinc finger and BTB domain-containing 7A (ZBTB7A) promotes bladder cancer (BC) by downregulating HIC1. Targeting ZBTB7A with miR-144-3p suppressed BC cell growth and tumor formation, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Zinc finger and BTB domain-containing 7A (ZBTB7A) has a dual role in cancer.
- Its function in bladder cancer (BC) is not well understood.
Purpose of the Study:
- To investigate the role and mechanism of ZBTB7A in bladder cancer.
- To explore the relationship between ZBTB7A, HIC1, and miR-144-3p in BC.
Main Methods:
- Cell growth, migration, and tumor formation assays were performed.
- Expression levels of ZBTB7A, HIC1, and miR-144-3p were analyzed.
- Bioinformatics and dual-luciferase reporter assays assessed ZBTB7A's effect on HIC1.
Main Results:
- ZBTB7A knockdown inhibited BC cell growth, migration, and tumor growth in vivo.
- ZBTB7A downregulated HIC1 expression by binding to its promoter.
- ZBTB7A expression inversely correlated with HIC1 expression in BC tissues.
- miR-144-3p targeted ZBTB7A, reducing its expression in BC.
Conclusions:
- ZBTB7A promotes bladder cancer tumorigenesis by downregulating HIC1.
- ZBTB7A is a target of miR-144-3p.
- This highlights a novel regulatory axis with therapeutic implications for BC.
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