Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer

Tumour Biol. 2016 Jul;37(7):8931-40. doi: 10.1007/s13277-015-4771-6. Epub 2016 Jan 11.

Abstract

Our previous studies have demonstrated overexpression of Mcl-1 in cervical cancer tumorigenesis. However, the molecular mechanism of its overexpression remains not elucidated. MiR-320 has been reported to be down-regulated in various types of cancer, and bioinformatics prediction indicated that it may regulate the expression of Mcl-1. The aim of this study is to investigate the role of miR-320 and its target gene Mcl-1 in cervical cancer progression and to assess their clinical significance. miR-320 and Mcl-1 expressions in human cervical cancer tissues were investigated by qRT-PCR, in situ hybridization, and immunohistochemical staining, respectively. The clinicopathological implications of these molecules were analyzed. Bioinformatic prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Mcl-1. The apoptosis, proliferation, migration, and invasion assays were performed to investigate the effect of miR-320 on the cervical cancer cells. MiR-320 expression is significantly down-regulated versus Mcl-1 expression is up-regulated in cervical cancer tissues compared with normal controls with a negative correlation between them. Luciferase assay showed that miR-320 negatively regulates Mcl-1 expression. In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells. Our studies show that miR-320 expression is decreased in cervical cancer, and its expression is negatively correlated with Mcl-1 expression in cervical cancer. In addition, miR-320 inhibits cervical cancer progression by down-regulation of Mcl-1. These results indicate that miR-320 may be an important biomarker and target for diagnosis and treatment of cervical cancer patient.

Keywords: Apoptosis; Cervical cancer; Mcl-1; miR-320.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Caspase 3 / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics*
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / parasitology*

Substances

  • MCL1 protein, human
  • MIRN320 microRNA, human
  • MicroRNAs
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Caspase 3