Inhibitory roles of miR‑9 on papillary thyroid cancer through targeting BRAF

Mol Med Rep. 2018 Jul;18(1):965-972. doi: 10.3892/mmr.2018.9010. Epub 2018 May 11.

Abstract

MicroRNA‑9 (miR‑9) is reported to be underexpressed in papillary thyroid carcinoma (PTC) tissues; however, the molecular mechanisms underlying the implication of miR‑9 in PTC have yet to be elucidated. The present study aimed to explore the potential roles of miR‑9 in PTC. PTC tissue samples and paired non‑cancerous adjacent tissues were collected from 60 patients with PTC. The human TPC‑1 thyroid gland papillary carcinoma cell line was used to investigate the molecular mechanisms underlying the roles of miR‑9 in PTC. The levels of miR‑9 and its downstream target gene BRAF were detected through reverse transcription‑quantitative polymerase chain reaction. MTT assay and flow cytometry were performed to evaluate cell viability and apoptosis, respectively. A mouse xenograft tumor model was established to observe the effects of miR‑9 on thyroid gland tumorigenesis in vivo. The present study revealed that the expression of miR‑9 was significantly reduced in PTC tissues compared with paired normal tissues. In addition, miR‑9 upregulation suppressed the expression of BRAF in TPC‑1 cells in vitro. Luciferase reporter assay demonstrated that BRAF may be a direct target gene of miR‑9 in TPC‑1 cells. In addition, following transfection with miR‑9 mimics, the viability of TPC‑1 cells was suppressed and their apoptosis was enhanced; conversely, transfection with miR‑9 inhibitor exerted the opposite effects in vitro. miR‑9 overexpression or downregulation also affected in vivo PTC tumorigenesis in athymic mice. The present findings suggested that miR‑9 may suppress the viability of PTC cells and inhibit tumor growth through directly targeting the expression of BRAF in PTC.

MeSH terms

  • Animals
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism*
  • Carcinoma, Papillary / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins B-raf / biosynthesis*
  • Proto-Oncogene Proteins B-raf / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology

Substances

  • MIRN92 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf