miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2

PLoS Genet. 2018 Dec 17;14(12):e1007790. doi: 10.1371/journal.pgen.1007790. eCollection 2018 Dec.

Abstract

Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclins / antagonists & inhibitors*
  • Cyclins / genetics
  • Down-Regulation
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis
  • Prognosis
  • RNA, Small Nucleolar / antagonists & inhibitors
  • RNA, Small Nucleolar / blood
  • RNA, Small Nucleolar / genetics*
  • Receptor, Transforming Growth Factor-beta Type I / antagonists & inhibitors*
  • Receptor, Transforming Growth Factor-beta Type I / genetics

Substances

  • Biomarkers, Tumor
  • CCNE2 protein, human
  • Cyclins
  • RNA, Small Nucleolar
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81402534), the Natural Science Foundation of Hebei province (No. H2015105095), the Young Top-Notch talent Project of Hebei province (No. JI2016(10), Talent Project of Hebei province (A2016002090, A201801005) and Medical Science Research and Key Project of Hebei province (ZD20140084). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.