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Tumor Biology

, Volume 36, Issue 6, pp 4357–4365 | Cite as

MicroRNA-15a induces cell apoptosis and inhibits metastasis by targeting BCL2L2 in non-small cell lung cancer

  • Tian Yang
  • Asmitananda Thakur
  • Tianjun Chen
  • Li Yang
  • Gao Lei
  • Yiqian Liang
  • Shuo Zhang
  • Hui Ren
  • Mingwei Chen
Research Article

Abstract

MicroRNAs (miRNAs) play a critical role in cancer development and progression. Aberrant expression of miR-15a has recently been reported in several cancers, but its role in non-small cell lung cancer (NSCLC) still remains obscure. We investigated the effects of miR-15a on proliferation, apoptosis, and metastasis in A549 cells. Eighteen paired NSCLC and adjacent non-tumor lung tissues were surgically removed and immediately snap frozen until total RNA was extracted and confirmed by two independent pathologists. The targets of miR-15a were predicted by bioinformatics tools. RNA isolation and quantitative real-time PCR (qRT-PCR), Western blot analysis, cell proliferation assay, cell cycle analysis, cell apoptosis assay, and migration and invasion assays were done. The wild type (WT) or mutant type (MT) 3′-untranslated region (UTR) vectors were co-transfected with miR-15a or negative control into A549 cells, and after 24 h of transfection, luciferase activity was measured using the Dual-Glo luciferase assay kit. Statistical analysis was performed using SPSS 13.0 software (SPSS, Chicago, IL, USA). P values of less than 0.05 were considered statistically significant. miR-15a was significantly downregulated in NSCLC than in adjacent non-cancerous tissues. miR-15a overexpression remarkably inhibited cell viability, invasion, and migration and promoted the apoptosis of NSCLC cells. Additionally, inhibition of miR-15a expression had the opposite effects on tumor progression, while cell cycle remained unaltered. Furthermore, we identified that BCL2L2 was a target of miR-15a and negatively regulated by miR-15a at the translational level. miR-15a acts as a tumor suppressor in NSCLC by directly targeting BCL2L2 and may serve as a potential diagnostic biomarker and therapeutic target for NSCLC.

Keywords

Non-small cell lung cancer miR-15a Apoptosis Metastasis BCL2L2 

Notes

Acknowledgments

This work was supported in part by a grant from Shaanxi Science and Technology Research Funds (Grant Number: 2011K12-15).

Conflicts of interest

None

Supplementary material

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Fig 8 (JPEG 74 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Tian Yang
    • 1
  • Asmitananda Thakur
    • 1
  • Tianjun Chen
    • 1
  • Li Yang
    • 1
  • Gao Lei
    • 1
  • Yiqian Liang
    • 1
  • Shuo Zhang
    • 1
  • Hui Ren
    • 1
  • Mingwei Chen
    • 1
  1. 1.Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, School of MedicineXi’an Jiaotong UniversityXi’anChina

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