Identification of serum miR-1915-3p and miR-455-3p as biomarkers for breast cancer

PLoS One. 2018 Jul 26;13(7):e0200716. doi: 10.1371/journal.pone.0200716. eCollection 2018.

Abstract

Breast cancer is one of the most malignant diseases in women worldwide. Serum microRNAs (miRNAs), with the characteristics of high sensitivity and specificity, have recently attracted more attentions to serve as potential biomarkers for tumor diseases. In this study, 194 breast cancer patients' serum samples were collected before surgery and enrolled into different groups based on their diagnostic information. To search for breast cancer diagnostic biomarkers, serum miRNAs were screened by microarray in pooled samples of healthy volunteers and breast cancer patients in different clinical stages. The miRNAs were further verified in each individual patient's serum samples in diagnostic and predictive sets. The serum level of miR-1915-3p was upregulated and miR-455-3p was downregulated significantly in breast cancer patients compared with healthy volunteers. Furthermore, the patients with infiltrating carcinoma or lymph node metastasis had a higher serum level of miR-1915-3p and lower serum level of miR-455-3p than patients with the carcinoma in situ or patients without lymph node metastasis. ROC analysis suggested that miR-1915-3p and miR-455-3p had the potential as a promising serum diagnostic and predictive biomarkers of breast cancer. miR-1915-3p was over-expressed in certain human breast cancer cells. Functional experiments in vitro showed that miR-1915-3p enhanced cell proliferative and migrational abilities. Overexpression of miR-1915-3p repressed target gene DUSP3 and activated ERK1/2. Collectively, this study provided a new insight that miR-1915-3p might play a role in the development of breast cancer and that serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Breast Carcinoma In Situ / blood
  • Breast Carcinoma In Situ / diagnosis*
  • Breast Carcinoma In Situ / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / metabolism
  • Down-Regulation
  • Dual Specificity Phosphatase 3 / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Healthy Volunteers
  • Humans
  • Lymphatic Metastasis
  • MAP Kinase Signaling System / genetics
  • MicroRNAs / blood*
  • MicroRNAs / metabolism
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MIRN1915 microRNA, human
  • MIRN455 microRNA, human
  • MicroRNAs
  • DUSP3 protein, human
  • Dual Specificity Phosphatase 3

Grant support

This work was supported by the National Natural Science Foundation of China (No. 81472654), http://www.nsfc.gov.cn/; the National Natural Science Foundation of China (No.81672914), http://www.nsfc.gov.cn/; the National Basic Research Program of China (No. 2013CB967202), http://program.most.gov.cn/.