MicroRNA‑195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer

Int J Mol Med. 2018 Aug;42(2):779-788. doi: 10.3892/ijmm.2018.3660. Epub 2018 May 8.

Abstract

MicroRNAs (miRs), a class of small non‑coding RNAs, have been demonstrated to perform promoting or suppressive roles in various types of human malignancy. Deregulation of miR‑195 has been observed in numerous types of human cancer, including cervical cancer; however, the detailed molecular mechanism of miR‑195 underlying the malignant progression of cervical cancer remains largely unclear. In the present study, miR‑195 was significantly downregulated in cervical cancer tissue samples compared with adjacent non‑tumor tissue samples, and the reduced expression level of miR‑195 was associated with node metastasis and an advanced clinical stage in cervical cancer. Furthermore, the patients with low miR‑195 expression levels demonstrated shorter survival times when compared with those with high miR‑195 expression levels. In vitro experiments indicated that miR‑195 exerted suppressive effects on the proliferation, migration and invasion of cervical cancer cells. Luciferase reporter gene assay identified defective in cullin neddylation 1 domain containing 1 (DCUN1D1) as a novel target gene of miR‑195 and the expression level of DCUN1D1 was identified to be negatively regulated by miR‑195 in cervical cancer cells. DCUN1D1 was significantly upregulated in cervical cancer, with a negative correlation to miR‑195 expression. Furthermore, upregulation of DCUN1D1 was associated with the malignant progression and poor prognosis of cervical cancer. DCUN1D1 overexpression attenuated the suppressive effects of miR‑195 on the malignant phenotypes of cervical cancer cells. Notably, the expression levels of miR‑195 were significantly lower in HeLa [human papilloma virus (HPV)18+] and SiHa (HPV16+) cells compared with those in C33A (HPV‑) cells, and knockdown of E6 using small interfering RNA significantly increased the miR‑195 expression while the DCUN1D1 expression level was reduced in HeLa and SiHa cells. Thus, these findings indicate that miR‑195 exerts a suppressive role in cervical cancer by targeting DCUN1D1. Therefore, miR‑195 may present as a potential therapeutic candidate for cervical cancer.

Publication types

  • Retracted Publication

MeSH terms

  • Cell Movement
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Proteins
  • Proto-Oncogene Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • DCUN1D1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN195 microRNA, human
  • MicroRNAs
  • Proteins
  • Proto-Oncogene Proteins