Connexin43 as a Tumor Suppressor: Proposed Connexin43 mRNA-circularRNAs-microRNAs Axis Towards Prevention and Early Detection in Breast Cancer.

Nataly Naser Al Deen,Mounir Abouhaidar,Rabih Talhouk

doi:10.3389/fmed.2019.00192

Nataly Naser Al Deen, Mounir Abouhaidar + Show 1 more

Open Access

https://doi.org/10.3389/fmed.2019.00192

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Abstract

Breast cancer (BC) is a global public health burden, constituting the highest cancer incidence in women worldwide. Connexin43 (Cx43) is a member of a family of transmembrane proteins responsible in part for intercellular communication between adjacent breast epithelial cells, via gap junctions. Cx43 plays key role in mammary gland development and differentiation and its spatio-temporal perturbation contributes to tumorigenesis. Thus, Cx43 acts as a breast tumor-suppressor. Signaling pathways and phenotypes downstream of Cx43 mRNA loss/mis-localization in breast cells have been well-studied. However, axes parallel to Cx43 loss are less understood. microRNAs (miRNAs) are small endogenous non-coding RNAs that repress translation and circularRNAs (circRNAs) are a class of endogenous RNAs that originate from RNA splicing and act as miRNA “sponges”. CircRNAs and miRNAs are dysregulated in cancers and are highly abundant and stable in the circulation. Thus, they present as attractive liquid biopsy cancer biomarkers. Here, an axis for Cx43 mRNA-circRNAs-miRNAs interactions along BC initiation (denoted by loss of breast epithelial polarity and development of hyperplastic phenotypes) is proposed to potentially serve as a signature biomarker toward BC early-onset detection and prevention.

Highlights

Breast cancer (BC) registers the highest incidence and mortality rates in females and is the second most commonly diagnosed cancer [1]
An axis by Cx43-derived circRNAs and their sponged miRNAs is proposed during BC initiation stages, which might act as promising biomarker signature toward BC early-onset detection and prevention, especially in patients at increased risk
We propose a possible biomarker signature axis of Cx43 mRNA-circRNAs-miRNAs in BC early-onset detection and prevention

Summary

Introduction

BC registers the highest incidence and mortality rates in females and is the second most commonly diagnosed cancer (after lung cancer) [1]. CircRNAs and miRNAs unique dysregulation signatures in cancers (in tissue- and development stagespecific manner), their tumor suppressive/oncogenic roles and stability and abundance in body fluids make them attractive non-invasive biomarkers in liquid biopsies [5, 27].

Results

Conclusion