Embigin, regulated by HOXC8, plays a suppressive role in breast tumorigenesis

Abstract

The transmembrane glycoprotein embigin (EMB) belongs to the immunoglobulin superfamily (IgSF) and a number of IgSF members have been identified as biomarkers for cancer progression. In this study, we show that embigin is transcriptionally regulated by Homeobox C8 (HOXC8) in breast cancer cells and embigin expression suppresses breast tumorigenesis. With aid of Western blot, luciferase reporter gene assay and chromatin immunoprecipitation, we reveal that HOXC8 binds to the EMB promoter at the region of nucleotides −2303 to −2315 and acts as a transcription inhibitor to suppress embigin expression. Depletion of embigin leads to increase in proliferation, anchorage-independent growth and migration of breast cancer cells, and the inhibitory effects mediated by HOXC8 knockdown on breast tumorigenesis can be largely rescued by depletion of embigin expression in breast cancer cells, suggesting that HOXC8 regulates breast tumorigenesis, at least partly, through regulating embigin expression. Moreover, we show that loss of embigin promotes proliferation, anchorage-independent growth, and migration ability of normal mammary epithelial MCF10A cells. The analyses of publically available human breast tumor microarray gene expression database show that low embigin levels correlate with short survival of breast tumor patients, particularly with basal-like tumor patients, and embigin expression is low specifically in patients with basal-like, ER-/HER2- tumors. Taken together, our study demonstrates that low/loss of embigin plays an important role in the progression of breast tumors.

Acfs: accurate circRNA identification and quantification from RNA-Seq data

“…3g). EMB (Embigin) encodes a transmembrane protein belonging to the immunoglobulin superfamily that has been identified as a biomarker for cancer progression35. In addition to the potential pathogenic role of circ_RMB, the conversion of linear EMB transcript to circRNAs via back-splicing might also serve to decrease the protein output and thereby lead to excessive cell proliferation.…”

Integration of lncRNA and mRNA Transcriptome Analyses Reveals Genes and Pathways Potentially Involved in Calf Intestinal Growth and Development during the Early Weeks of Life

“…LY6D protein initiates the first stage of B cell development [ 57 ] while MUC1 protein plays important roles in the first line defense against invading pathogens [ 58 ]. Meanwhile, EMB and EYA2 have important roles in development processes [ 59 , 60 ]. As expected, DE genes were enriched in many biological processes related to regulation of biological and cellular processes, which reflect the major developmental changes in the physiology and functions of the rumen from pre- to post-weaning stages ( Figure 1 ).…”

Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration

“…As a member of the HOX family, HOXC8 functions as a transcriptional activator to induce the expression of several genes, including osteopontin (OPN), neural cell adhesion molecule (NCAM), proliferating cell nuclear antigen (PCNA), and CDH11 [ 33 , 34 ]. It has also been reported that HOXC8 acts as a transcriptional repressor to downregulate the expression of Mgl1, Smad6 and embigin [ 35 – 37 ]. Since CDH11 is expressed only in invasive breast cancer cells and HOXC8 acts as either a transcriptional activator or repressor, we speculated that HOXC8 associated with other proteins to activate CDH11 transcription in breast cancer cells.…”