Research Paper Volume 11, Issue 9 pp 2628—2652

Five miRNAs-mediated PIEZO2 downregulation, accompanied with activation of Hedgehog signaling pathway, predicts poor prognosis of breast cancer

Weiyang Lou 1, *, , Jingxing Liu 2, *, , Bisha Ding 1, , Luqi Jin 4, , Liang Xu 1, , Xia Li 3, , Jing Chen 3, , Weimin Fan 1, ,

  • 1 Program of Innovative Cancer Therapeutics, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou 313100, China
  • 2 Department of Intensive Care Unit, Changxing People’s Hospital of Zhejiang Province, Huzhou 313100, China
  • 3 First Affiliated Hospital of Jiaxing University, Zhejiang Province, Jiaxing 314000, China
  • 4 The National Education Base for Basic Medical Sciences, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou 310058, China
* Equal contribution

received: November 26, 2018 ; accepted: April 23, 2019 ; published: May 6, 2019 ;

https://doi.org/10.18632/aging.101934
How to Cite

Copyright: Lou et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Roles of Piezo-type mechanosensitive ion channel component 2 (PIEZO2) in cancer remain largely unknown. Herein, we explored PIEZO2 expression, prognosis and underlying mechanisms in cancer. Breast was selected as the candidate as its relatively higher expression level of PIEZO2 than other human tissues. Next, we identified a decreased expression of PIEZO2 in breast cancer compared with normal controls, and found that PIEZO2 expression positively correlated with estrogen receptor (ER) and progesterone receptor (PR) status but negatively correlated with human epidermal growth factor receptor 2 (HER2) status, Nottingham Prognostic Index (NPI) score, Scarff-Bloom-Richardson (SBR) grade, basal-like and triple-negative status. Subsequent analysis revealed that high expression of PIEZO2 had a favorable prognosis in breast cancer. 182 miRNAs were predicted to target PIEZO2. Among these miRNAs, five miRNAs (miR-130b-3p, miR-196a-5p, miR-301a-3p, miR-421 and miR-454-3p) possess the greatest potential in targeting PIEZO2. 109 co-expressed genes of PIEZO2 were identified. Pathway enrichment analysis showed that these genes were enriched in Hedgehog signaling pathway, including Cell adhesion molecule-related/downregulated by oncogenes (CDON). CDON expression was decreased in breast cancer and downregulation of CDON indicated a poor prognosis. Altogether, these findings suggest that decreased expression of PIEZO2 may be utilized as a prognostic biomarker of breast cancer.

Abbreviations

CDON: Cell adhesion molecule-related/downregulated by oncogenes; CI: confidence interval; ER: estrogen receptor; GAPDH: Glyceralddehyde-2-phosphate dehydrogenase; GO: Gene Ontology; HER2: human epidermal growth factor receptor 2; HPA: Human Protein Atlas; HR: hazard ratio; PIEZO2: piezo-type mechanosensitive ion channel component 2; NPI: Nottingham Prognostic Index; PR: progesterone receptor; SBR: Scarff-Bloom-Richardson; TCGA: The Cancer Genome Atlas.