Tumor Biology

, Volume 37, Issue 5, pp 5821–5828 | Cite as

MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF

Original Article

Abstract

We examined the expression pattern and functional roles of microRNA 15a-5p (miR-15a-5p) in human hepatocellular carcinoma (HCC). Possible miR-15a-5p aberrant expression in HCC cell lines or clinical HCC specimens was examined by quantitative real-time PCR (qRT-PCR). In HCC HepG2 and SNU-182 cells, miR-15a-5p was ectopically overexpressed by lentiviral transduction. Its effect on HCC proliferation, cancer division, and in vivo tumor growth were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, and tumorigenicity assay, respectively. The targeting of miR-15a-5p on its downstream gene, brain-derived neurotrophic factor (BDNF), was examined by dual-luciferase assay, qRT-PCR, and Western blot, respectively. BDNF was then overexpressed in HepG2 and SNU-182 cells to evaluate its selective effect on miR-15a-5p in HCC modulation. MiR-15a-5p is aberrantly downregulated in in vitro HCC cell lines and in vivo HCC clinical specimens. Ectopic overexpression of miR-15a-5p suppressed cancer proliferation, induced cell cycle arrest in HepG2 or SNU-182 cells in vitro, and inhibited HCC tumor growth in vivo. MiR-15a-5p selectively and negatively regulated BDNF at both gene and protein levels in HCC cells. Forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-15a-5p on HCC proliferation and cell division in vitro. Our study demonstrated that miR-15a-5p is a tumor suppressor in HCC and its regulation is through BDNF in HCC.

Keywords

Hepatocellular carcinoma miR-15a-5p BDNF Cancer proliferation Cell cycle 

Notes

Acknowledgments

This work was supported by the Science and Technology Planning Project of Guangdong Province (2013B021800284) and the National Natural Science Foundation of China (Nos. 81272312, 81300421).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Medicinal OncologyThe First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouChina
  2. 2.Department of Hepatobiliary Surgery, Division of Interventional UltrasoundThe First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouChina
  3. 3.Department of Medical Ultrasonics, Institute of Diagnostic and Interventional UltrasoundThe First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouChina
  4. 4.Department of Clinic NutritionThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

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