Epigenetic Regulation of CDH1 Is Altered after HOXB7-Silencing in MDA-MB-468 Triple-Negative Breast Cancer Cells

Abstract

HOXB7 is often overexpressed in breast cancer cells and found to relate to poor prognosis. The search for the HOXB7 targets, as a transcription factor, has led to molecules involved in regulating cell proliferation, migration, invasion, and processes such as angiogenesis and therapy resistance. However, the specific targets affected by the deregulation of HOXB7 in breast cancer remain largely unknown in most molecular sub-types, such as triple-negative breast cancers (TNBC). To unveil the molecular basis behind these aggressive and often untreatable cancers, here we explored the contribution of HOXB7 deregulation for their aggressiveness. To this end, HOXB7 was silenced in TNBC Basal A cells MDA-MB-468, and the phenotype, gene/protein expression, and methylation profile of putative targets were analyzed. Lower migration and invasion rates were detected in HOXB7-silenced cells in comparison with the controls. In addition, these cells expressed more CDH1 and less DNMT3B, and the promoter methylation status of CDH1 diminished. Our data suggest that the HOXB7 transcription factor may act on TNBC Basal A cells by controlling CDH1 epigenetic regulation. This may occur indirectly through the up-regulation of DNMT3B, which then controls DNA methylation of the CDH1 promoter. Thus, future approaches interfering with HOXB7 regulation may be promising therapeutic strategies in TNBC treatment.

MIR143HG promotes methylation of transcription factor HOXB7 promoter by recruiting methyltransferase DNMT1 to prevent the progression of colon cancer

“…The Hyman team detected HOXB7 amplification in 10% of the 363 cases of breast cancer and found a direct correlation between amplification and poor prognosis 40 . Additionally, studies have reported that inhibiting HOXB7 expression in MDA‐MB‐468 triple‐negative breast cancer can regulate the expression of CDH1 through epigenetic mechanisms, thereby modulating the metastatic potential of breast cancer 27 . After correlation analysis, MIR143HG was found to be negatively related to HOXB7 (Figure 3A).…”

“…40 Additionally, studies have reported that inhibiting HOXB7 expression in MDA-MB-468 triple-negative breast cancer can regulate the expression of CDH1 through epigenetic mechanisms, thereby modulating the metastatic potential of breast cancer. 27 After correlation analysis, MIR143HG was found to be negatively related to HOXB7 (Figure 3A). As shown in Figure 3B, HOXB7 was highly expressed in colon cancer-related RNAseq data in the TCGA database.…”

“…26 The HOXB7 transcription factor may impact the overexpression and prognosis of cancer cells by controlling the DNA methylation of the DNMT promoter. 27 Furthermore, there is literature reporting that HOXB13 can regulate the occurrence and development of glioma through DNMT-mediated methylation. 28 DNMT-mediated methylation can modulate gene expression patterns, including the repression of tumor suppressor genes.…”

“…Furthermore, emerging evidence suggests that HOXB7 may be regulated through DNA methylation, specifically through interactions with DNMT proteins 26 . The HOXB7 transcription factor may impact the overexpression and prognosis of cancer cells by controlling the DNA methylation of the DNMT promoter 27 . Furthermore, there is literature reporting that HOXB13 can regulate the occurrence and development of glioma through DNMT‐mediated methylation 28 .…”

The analysis of tumor-infiltrating immune cell and ceRNA networks in laryngeal squamous cell carcinoma

“…For example, HOXB7 is highly expressed in breast cancer, ovarian cancer, and melanoma samples. [42][43][44][45] STC2 is highly expressed in rectal cancer and colon cancer. [46,47] TMEM158 is upregulated in laryngeal cancer, glioblastoma, and colorectal cancer.…”