miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer

Yilin Wang; Xiaolong Zhang; Chao Zou; Hsiang-Fu Kung; Marie C Lin; Andreas Dress; Fiona Wardle; Bing-Hua Jiang; Lihui Lai

doi:10.1016/j.biopha.2016.03.007

miR-195 inhibits tumor growth and angiogenesis through modulating IRS1 in breast cancer

Biomed Pharmacother. 2016 May:80:95-101. doi: 10.1016/j.biopha.2016.03.007. Epub 2016 Mar 17.

Authors

Yilin Wang¹, Xiaolong Zhang¹, Chao Zou¹, Hsiang-Fu Kung², Marie C Lin³, Andreas Dress⁴, Fiona Wardle⁵, Bing-Hua Jiang⁶, Lihui Lai⁷

Affiliations

¹ Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
² Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
³ Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; Brain Tumor Center, Neurosurgery Division, Faculty of Medicine, PWH, The Chinese University of Hong Kong, Shatin, Hong Kong.
⁴ Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; CAS-MPG Partner Institute and Key Lab for Computational Biology, SIBS, CAS, Shanghai, China.
⁵ Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China; Randall Division of Cell and Molecular Biophysics, New Hunt's House, King's College of London, Guy's Campus, London SE1 1UL, UK.
⁶ State Key Lab of Reproductive Medicine, and Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
⁷ Department of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China. Electronic address: lhlai@bio.ecnu.edu.cn.

PMID: 27133044
DOI: 10.1016/j.biopha.2016.03.007

Abstract

Angiogenesis has been found as an attractive target for drug therapy as it is necessary for tumor growth. Accumulating evidences show that microRNAs (miRNAs), which are a group of highly conserved, single-stranded, short non-coding RNAs, play important roles through directly targeting angiogenic factors and protein kinases. The purpose of this study is to investigate the role of miR-195 in breast cancer development and angiogenesis through targeting IRS1. We show that miR-195 is inversely related with Insulin receptor substrate 1 (IRS1) in both breast cancer cells and breast cancer tissues. Induction of miR-195 could suppress IRS1 protein expression through binding to its 3'UTR regions either by transfection with miR-195 oligo or by infection with lentivirus encoding miR-195 gene. Moreover, re-expression of IRS1 reverses miR-195-mediated repression of tumor cell growth and miR-195 inhibits tumor angiogenesis through suppressing IRS1-VEGF axis. These data suggest that miR-195 mimics are potential therapeutic agents for breast cancer diagnose.

Keywords: Angiogenesis; Breast cancer; Insulin receptor substrate 1; MiR-195.

MeSH terms

Animals
Base Sequence
Breast Neoplasms / blood supply*
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation
Chickens
Down-Regulation / genetics
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Insulin Receptor Substrate Proteins / genetics*
Insulin Receptor Substrate Proteins / metabolism
MicroRNAs / metabolism*
Neovascularization, Pathologic / genetics*
Reproducibility of Results

Substances

Insulin Receptor Substrate Proteins
MIRN195 microRNA, human
MicroRNAs