MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL)

Oncol Res. 2018 Aug 23;26(7):987-996. doi: 10.3727/096504017X15140534417184. Epub 2018 Jan 2.

Abstract

Cervical cancer is the fourth most common malignancy among females worldwide. MicroRNA-379 (miR-379) is aberrantly expressed in multiple human cancer types. However, the expression pattern, roles, and detailed regulatory mechanisms of miR-379 in cervical cancer remain unknown. In this study, we found that miR-379 expression was downregulated in cervical cancer tissues and cell lines. Low miR-379 expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis. Additionally, miR-379 overexpression suppressed the proliferation and invasion of cervical cancer cells. Furthermore, V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) was identified as a direct target of miR-379 in cervical cancer. CRKL was upregulated in cancer tissues and negatively correlated with miR-379 expression. Moreover, restored CRKL expression rescued the inhibitory effects of miR-379 overexpression on cell proliferation and invasion. In conclusion, miR-379 may serve as a tumor suppressor in cervical cancer by directly targeting CRKL. Restoring miR-379 expression may be an effective strategy for the treatment of cervical cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary*
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Middle Aged
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CRKL protein
  • MIRN379 microRNA, human
  • MicroRNAs
  • Nuclear Proteins