MicroRNA-150 targets Rho-associated protein kinase 1 to inhibit cell proliferation, migration and invasion in papillary thyroid carcinoma

Mol Med Rep. 2017 Aug;16(2):2217-2224. doi: 10.3892/mmr.2017.6842. Epub 2017 Jun 22.

Abstract

Thyroid cancer is the most prevalent malignant tumor of the endocrine organs and accounts for one third of all head and neck tumors. Dysregulation of microRNAs is well‑known to contribute to the development of various cancers, including papillary thyroid carcinoma (PTC), which accounts for 80‑90% of all thyroid cancer cases. The present study aimed to investigate the expression, functional roles of microRNA‑150 (miR‑150) and its direct target gene in PTC. miR‑150 expression in PTC tissues and cell lines was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). After transfection with miR‑150 mimics, cell proliferation, migration and invasion was analyzed by MTT and Transwell assays, respectively. Bioinformatics analysis was performed to investigate the potential target genes of miR‑150, which were then confirmed by luciferase reporter assay, RT‑qPCR and western blotting. Functional assays were also applied to investigate the effects of endogenous Rho‑associated protein kinase 1 (ROCK1) in PTC. miR‑150 was demonstrated to be significantly downregulated in PTC tissues and cell lines. In addition, reduced miR‑150 expression was obviously correlated with TNM stage and lymph node metastasis in PTC patients. Restoration of miR‑150 expression significantly inhibited PTC cell proliferation, migration and invasion in vitro. Furthermore, ROCK1 was identified as a direct target gene of miR‑150. Therefore, ROCK1 knockdown may serve tumor suppressive functions in PTC, induced by miR‑150 overexpression. In conclusion, miR‑150 overexpression in PTC may inhibit growth and metastasis of PTC cells. miR‑150/ROCK1‑based targeted therapy may be a potential strategy for the treatment of PTC.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Antagomirs / metabolism
  • Base Sequence
  • Carcinoma, Papillary / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Female
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / pathology*
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN150 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • ROCK1 protein, human
  • rho-Associated Kinases