circRNA‑CER mediates malignant progression of breast cancer through targeting the miR‑136/MMP13 axis

Mol Med Rep. 2019 Apr;19(4):3314-3320. doi: 10.3892/mmr.2019.9965. Epub 2019 Feb 18.

Abstract

Chondrocyte extracellular matrix‑related circular RNAs (circRNA‑CER) have been demonstrated to be involved in various diseases. However, its role in the development of human breast cancer is not clearly understood. The aims of the present study were to assess circRNA‑CER expression in paired cancer tissue and adjacent non‑tumor tissue from 24 patients with breast cancer, and to explore the roles and mechanisms by which circRNA‑CER mediates the malignant progression of breast cancer cells. The results revealed that circRNA‑CER and matrix metalloproteinase 13 (MMP13) were upregulated, whereas miR‑136 was downregulated in breast cancer tissues compared with adjacent non‑tumor tissues. In vitro silencing of circRNA‑CER using small interfering RNA (siRNA) had inhibitory effects on MCF‑7 breast cancer cell proliferation and migration, and similar results were obtained following overexpression of microRNA (miR)‑136 in MCF‑7 cells by transfection with miR‑136 mimics. The subsequent mechanistic study revealed that the expression levels of MMP13 were significantly lower in MCF‑7 cells following transfection with miR‑136 mimics, and silencing of circRNA‑CER enhanced miR‑136 and decreased MMP13 expression levels. Furthermore, silencing of miR‑136 by transfection with miR‑136 inhibitors resulted in an increase in MCF‑7 cell proliferation and migration. miR‑136 inhibitor‑derived biological effects were reversed by co‑transfection of cells with miR‑136 inhibitors and circRNA‑CER siRNA. Taken together, the present results suggested that circRNA‑CER may serve an important role in the progression of breast cancer by regulating the activity of the miR‑136/MMP13 axis, and may be a potential biomarker for the prediction and treatment of breast cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 13 / genetics*
  • Matrix Metalloproteinase 13 / metabolism
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA / genetics*
  • RNA Interference*
  • RNA, Circular

Substances

  • Biomarkers, Tumor
  • MIRN136 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA
  • MMP13 protein, human
  • Matrix Metalloproteinase 13