Oncogenic HBXIP enhances ZEB1 through Sp1 to accelerate breast cancer growth

Abstract

BackgroundThere is abundant evidence to indicate that HBXIP functions as an oncoprotein and transcription co‐activator during the development and promotion of cancers. In multiple cancers, ZEB1 serves as a transcription activator to regulate gene expression. We explored the roles of ZEB1 in HBXIP‐induced breast cancer growth.MethodsHBXIP regulation of ZEB1 was evaluated by reverse transcription PCR and immunoblotting. The stimulation of ZEB1 promoter by HBXIP and/or Sp1 was tested using luciferase reporter gene analysis. The alteration of cell proliferation mediated by HBXIP‐induced ZEB1 was tested using methyl‐thiazolyl‐tetrazolium and 5‐Ethynyl‐2′‐deoxyuridine (EdU) incorporation analysis. ZEB1 and HBXIP expression in human breast cancer tissues was analyzed using quantitative real‐time PCR. The relationship between HBXIP and ZEB1 was confirmed by Pearson's correlation coefficient.ResultsWe observed dose‐dependent upregulation of ZEB1 by HBXIP in breast cancer cells. HBXIP can activate the ZEB1 promoter by interacting with transcription factor Sp1. Cell viability and EdU incorporation analysis showed that HBXIP could drive cell proliferation by enhancing ZEB1 in breast cancer. Using quantitative real‐time PCR, ZEB1 overexpression and a positive relationship between ZEB1 and HBXIP were observed in clinical breast cancer samples.ConclusionOncogenic HBXIP controls the transcription regulation of ZEB1 by co‐activating Sp1, thereby accelerating breast cancer growth.

Retracted: MicroRNA‐4429 restrains colorectal cancer cell invasion and migration via regulating SMAD3‐induced epithelial–mesenchymal transition

“…Transcription factors are generally known as regulators of genes at the transcriptional level (Jiang et al, 2018; Joo et al, 2017; Warfield et al, 2017). For instance, STAT3 facilitates AGC kinases activity in melanoma by transactivation of PDK1 (Picco et al, 2019).…”

Identification of potential microRNA diagnostic panels and uncovering regulatory mechanisms in breast cancer pathogenesis

“…Moreover, STAT3 up-regulates c-MYC, Cyclin D-1 and Bcl-2 target genes, involved in anti-apoptosis, survival and proliferation of BC cells 88 . Several studies have experimentally proved that SP1 has a crucial role in BC initiation and progression 89 – 91 . Furthermore, the genes with the largest degree value were CCND1, VEGFA, MMP9, PTEN and MMP2.…”

Construction of a Potential Breast Cancer-Related miRNA-mRNA Regulatory Network

“…Some miRNAs confirmed by earlier studies can also be found in our network. For example, miR-335 inhibits the migration of BRCA cells through targeting oncoprotein c-Met [ 50 ]; miR-202 inhibits cell proliferation, invasion, and migration in BRCA by targeting the ROCK1 gene [ 51 ]; miR-381 inhibits BRCA cell proliferation, epithelial-to-mesenchymal transition, and metastasis by targeting CXCR4 [ 52 ]; miRNA-205 inhibits the proliferation and invasion of BRCA by regulating AMOT expression [ 53 ]; miR-145-5p suppresses BRCA progression by inhibiting SOX2 [ 54 ]; miR-378 mediates the metabolic shift in BRCA cells via the PGC-1 β /ERR γ transcriptional pathway [ 55 ]; miR-143 inhibits the metastasis and invasion of BRCA cells [ 56 ]; miRNA-154 inhibits the growth and invasion of BRCA cells through targeting E2F5 [ 57 ]; and mir-183 promotes proliferation and migration in BRCA cell lines [ 58 ]. However, miR-99, miR-376a, and miR-7 have no direct functional verification studies in BRCA.…”