microRNA-150 promotes cervical cancer cell growth and survival by targeting FOXO4

BMC Mol Biol. 2015 Dec 29:16:24. doi: 10.1186/s12867-015-0052-6.

Abstract

Background: Dysregulation of microRNA-150 (miR-150) is commonly observed in solid tumor and has been reported to be involved in multiple important biological processes, such as cell proliferation, apoptosis, and metastasis. Elevated miR-150 level was also detected in cervical carcinoma, whereas its function in cancer progression has not been studied yet.

Methods: The expression of miRNA-150 in cervical carcinoma was compared with normal cervical tissue and using qRT-PCR. The effects of miR-150 on cell cycle and apoptosis, as well as the expression of cycle- and apoptosis-related genes, were determined using flow cytometry, TUNEL assay, qRT-PCR, and Western blot, respectively. The direct target of miR-150 was confirmed using 3' untranslated region (UTR) luciferase reporter assay.

Results: miR-150 promotes cervical cancer cell survival and growth, while the inhibition of miR-150 suppresses these actions. miR-150 also induced the cell cycle progression from G1/G0 to S phase, resulting in an enhancement of growth. Several cell cycle- and apoptosis-related genes, CyclinD1, p27, BIM, and FASL were modulated by miR-150. Moreover, miR-150 directly reduced the expression of FOXO4, which regulates the expression of CyclinD1, p27, BIM, and FASL, by targeting its 3' UTR.

Conclusion: Taken together, our data demonstrated that elevated miR-150 targets FOXO4 expression and therefore regulates multiple genes expression, resulting in cervical cancer cell growth and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Bcl-2-Like Protein 11
  • Cell Cycle / genetics
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cell Survival / genetics*
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Fas Ligand Protein / metabolism
  • Female
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Neoplastic / genetics*
  • HEK293 Cells
  • Humans
  • In Situ Nick-End Labeling
  • Membrane Proteins / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Neoplasm Metastasis / genetics
  • Proto-Oncogene Proteins / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • CCND1 protein, human
  • CDKN1B protein, human
  • Cell Cycle Proteins
  • FASLG protein, human
  • FOXO4 protein, human
  • Fas Ligand Protein
  • Forkhead Transcription Factors
  • MIRN150 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27

Associated data

  • GEO/GSE30656