MicroRNA-411 Inhibits Cervical Cancer Progression by Directly Targeting STAT3

Oncol Res. 2019 Feb 21;27(3):349-358. doi: 10.3727/096504018X15247361080118. Epub 2018 May 1.

Abstract

Cervical cancer is the third most common gynecological cancer and the fourth leading cause of cancer-related deaths in women around the world. Substantial evidence has demonstrated that microRNA (miRNA) expression is disordered in many malignant tumors. The dysregulation of miRNAs has been suggested to be involved in the tumorigenesis and tumor development of cervical cancer. Therefore, identification of miRNAs and their biological roles and targets involved in tumor pathology would provide valuable insight into the diagnosis and treatment of patients with cervical cancer. MicroRNA-411 (miR-411) has been reported to play an important role in several types of human cancer. However, the expression level, role, and underlying molecular mechanisms of miR-411 in cervical cancer remain unclear. Therefore, the objectives of this study were to investigate the expression pattern and clinical significance of miR-411 in cervical cancer and to evaluate its role and underlying mechanisms in this disease. In this study, we confirmed that the expression of miR-411 was significantly downregulated in both cervical cancer tissues and cell lines. Low expression of miR-411 was associated with tumor size, FIGO stage, lymph node metastasis, and distant metastasis. Additionally, miR-411 overexpression inhibited cell proliferation and invasion in cervical cancer. Furthermore, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-411 in this disease. In clinical samples, miR-411 expression levels were inversely correlated with STAT3, which was significantly upregulated in cervical cancer. Restored STAT3 expression abolished the tumor-suppressing effects of miR-411 overexpression on the proliferation and invasion of cervical cancer cells. In conclusion, our data demonstrated that miR-411 inhibited cervical cancer progression by directly targeting STAT3 and may represent a novel potential therapeutic target and prognostic marker for patients with this disease.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Tumor Suppressor / physiology
  • HeLa Cells
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • STAT3 Transcription Factor / genetics*
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN411 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human