Interactive role of miR-126 on VEGF-A and progression of papillary and undifferentiated thyroid carcinoma

Hum Pathol. 2016 May:51:75-85. doi: 10.1016/j.humpath.2015.12.018. Epub 2016 Jan 7.

Abstract

MicroRNA-126 (miR-126) expression has been shown to be associated with angiogenesis. The aim of the current study is to evaluate the functional roles of miR-126 in dysregulation of VEGF expression and cancer progression in thyroid carcinomas. The expression of VEGF-A and miR-126 were measured in 101 thyroid carcinomas tissues (including 51 conventional papillary thyroid carcinoma, 37 follicular variant of papillary thyroid carcinoma, and 13 undifferentiated thyroid carcinomas), 13 matched lymph nodes with metastatic thyroid carcinoma, 21 benign thyroid tissues, and 5 thyroid carcinoma cell lines (both papillary and undifferentiated carcinomas). Then, exogenous miR-126 was transfected, and the expressions of VEGF-A were determined (Western blot technique). Proliferation assay, cell cycle analysis, and apoptosis assays were used to evaluate the role of miR-126 in these events. Significant underexpression of miR-126 levels in thyroid cancer tissues and cell lines was detected using real-time polymerase chain reaction. Introducing exogenous miR-126 into the cancer cell lines resulted in a significant reduction of VEGF-A protein expression. Marked inhibition in proliferation, cell cycle arrest in G0-G1, and promotion of total apoptosis were also noted. The modulatory role of miR-126 on expression of VEGF-A and its tumor suppressive roles were demonstrated for the first time in thyroid cancer. The current experiments provided specific information on the functional consequences of VEGF manipulation via microRNA on cancer.

Keywords: MicroRNA; Papillary thyroid carcinoma; Undifferentiated thyroid carcinoma; VEGF; miR-126.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma / blood supply
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood supply
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • Transfection
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • MIRN126 microRNA, human
  • MicroRNAs
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A