MiR-145 inhibits metastasis by targeting fascin actin-bundling protein 1 in nasopharyngeal carcinoma

PLoS One. 2015 Mar 27;10(3):e0122228. doi: 10.1371/journal.pone.0122228. eCollection 2015.

Abstract

Background: Based on our recent microarray analysis, we found that miR-145 was obviously downregulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its function and mechanism involving in NPC development and progression.

Methods: Quantitative RT-PCR was used to detect miR-145 expression in NPC cell lines and clinical samples. Wound healing, Transwell migration and invasion, three-dimension spheroid invasion assays, and lung metastasis model were performed to test the migratory, invasive, and metastatic ability of NPC cells. Luciferase reporter assay, quantitative RT-PCR, and Western blotting were used to verify the target of miR-145.

Results: MiR-145 was obviously decreased in NPC cell lines and clinical samples (P<0.01). Ectopic overexpression of miR-145 significantly inhibited the migratory and invasive ability of SUNE-1 and CNE-2 cells. In addition, stably overexpressing of miR-145 in SUNE-1 cells could remarkably restrain the formation of metastatic nodes in the lungs of mice. Furthermore, fascin actin-bundling protein 1 (FSCN1) was verified as a target of miR-145, and silencing FSCN1 with small RNA interfering RNA could suppress NPC cell migration and invasion.

Conclusions: Our findings demonstrated that miR-145 function as a tumor suppressor in NPC development and progression via targeting FSCN1, which could sever as a potential novel therapeutic target for patients with NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Female
  • Gene Silencing
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Metastasis

Substances

  • Carrier Proteins
  • FSCN1 protein, human
  • MIRN145 microRNA, human
  • MicroRNAs
  • Microfilament Proteins

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81402516; NL), the Pearl River Science and Technology New Star of Guangzhou, China (2015; NL), the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10; JM), the Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001; JM), and the Key Laboratory Construction Project of Guangzhou City (121800085; JM). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.