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

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. Conclusion Our data demonstrate that ZBTB7A, a targeted gene of miR-144-3p, promoted tumorigenesis of BC through downregulating HIC1 expression.

“Crosstalk between non-coding RNAs and transcription factor LRF in non-small cell lung cancer”

“…Finally, the 3ʹUTR of ZBTB7A -mRNA sequence encompasses a putative binding site for miR-144-3p. In bladder cancer miR-144-3p suppresses malignancy via targeting and decreasing ZBTB7A , having an inverse correlation with HIC1/ZBTB29 (Hypermethylated in cancer 1/Zinc Finger And BTB Domain-Containing Protein 29) gene expression [ 44 ], another member of the Zinc-Finger/BTB-Domain-Containing Proteins. In lung cancer increased expression of ZBTB7A has been shown to inactivate the TP53 (Tumor Protein P53) by increasing the levels of MDM2 (MDM2 Proto-Oncogene, E3 Ubiquitin Protein Ligase), frequently overexpressed in this type of malignancy.…”

Epigenetic Signatures of In Vitro and In Vivo Experimental Models Employed <span aria-describedby="tippy-29">in Non-small Cell Lung Cancer and the Unique miR-148b-3p/PVT1/ZBTB7A Regulatory Network Discriminating Large Cell Lung Carcinoma

“…Relative lower expression of hsa-miR-100, a direct suppressor of ZBTB7A, has been positively correlated with lymph node metastasis and lager tumor size in gastric cancer implying another emerging cooperation between miRs and transcription factors [43]. Also, A549 human cell line displayed downregulation of hsa-miR-20a-5p (Table 3), member of the miR-17 mammalian family and miR17/92 cluster, implicated in lung cancer in humans [46]. Hsa-miR-15a-5p, member of miR-15 mammalian family was downregulated in both A549 and H460 cell lines (Table 3) and mmu-miR-195a-5p, member of the same family was also downregulated (Table 2).…”

“…Finally, the 3'UTR of ZBTB7A-mRNA sequence encompasses a putative binding site for miR-144-3p. In bladder cancer miR-144-3p suppresses malignancy via targeting and decreasing ZBTB7A, having an inverse correlation with HIC1/ZBTB29 (Hypermethylated in cancer 1/Zinc Finger And BTB Domain-Containing Protein 29) gene expression [46], another member of the Zinc-Finger/BTB-Domain-Containing Proteins. In lung cancer increased expression of ZBTB7A has been shown to inactivate the TP53 (Tumor Protein P53) by increasing the levels of MDM2 (MDM2 Proto-Oncogene, E3 Ubiquitin Protein Ligase), frequently overexpressed in this type of malignancy.…”

Oral squamous cell carcinomas: state of the field and emerging directions

“…[264][265][266] miR-372 is overexpressed in OSCC and inhibits zinc finger and BTB domain-containing 7A protein (ZBTB7A), promoting tumorigenesis and CDDP resistance in OSCC cells. 267,268 OSCC cells and tissues overexpress the lncRNA HOXA11-AS relative to adjacent normal tissues and oral keratinocytes. 269 lncRNA HOXA11-AS consumes miR-98-5p, which is capable of inhibiting OSCC cell proliferation, 270 and suppresses miR-214-3p expression, which may lead to the establishment of drug resistance in OSCC.…”