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Front. Med. | doi: 10.3389/fmed.2019.00192

Title: Connexin43 as a tumor suppressor: Proposed Connexin43 mRNA-circularRNAs-microRNAs axis towards prevention and early detection in breast cancer

  • 1American University of Beirut, Lebanon
  • 2University of Toronto, Canada

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 towards BC early-onset detection and prevention.

Keywords: Gap junctions - connexins, breast cancer, MicroRNAs, CircularRNAs, tumor-suppressors, biomarkers, prevention

Received: 01 May 2019; Accepted: 14 Aug 2019.

Copyright: © 2019 Naser Al Deen, AbouHaidar and Talhouk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Rabih S. Talhouk, American University of Beirut, Beirut, 1107 2020, Beirut, Lebanon,