Circular RNA OMA1 regulates the progression of breast cancer via modulation of the miR‑1276/SIRT4 axis

Mol Med Rep. 2021 Oct;24(4):728. doi: 10.3892/mmr.2021.12367. Epub 2021 Aug 20.

Abstract

Mounting evidence has indicated that circular RNAs (circRNAs) serve essential roles in the tumorigenesis and development of various types of cancer. However, the biological functions and the underlying mechanisms of circRNAs in breast cancer (BC) remain largely elusive. In the present study, the expression pattern of circRNAs in three pairs of BC tissues and adjacent normal tissues was determined using a circRNA microarray. The expression and prognostic value of circOMA1 were evaluated by reverse transcription‑quantitative PCR in 64 pairs of BC tissues and adjacent normal tissues. Survival curves were generated by the Kaplan‑Meier method, and statistical significance was estimated using the log‑rank test. A series of in vitro functional experiments were then performed to investigate the role of circOMA1 in the tumorigenesis of BC. The results revealed that the expression levels of circOMA1 were upregulated in BC tissues, and its expression was markedly associated with tumor size and lymph node metastasis. Receiver operating characteristic analysis demonstrated that the expression of circOMA1 could be used to discriminate between BC tissues and adjacent normal tissues. Functionally, overexpression of circOMA1 promoted the viability, migration and invasion of BC cells, whereas circOMA1 knockdown had the opposite effect. Mechanistic investigations showed that circOMA1 promoted the progression of BC by sponging microRNA (miR)‑1276 and upregulating sirtuin 4 (SIRT4) expression. In conclusion, circOMA1 may act as an oncogenic circRNA in BC via regulation of the miR‑1276/SIRT4 axis.

Keywords: breast cancer; circular RNA OMA1; microRNA‑1276; sirtuin 4.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Prognosis
  • RNA, Circular*
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN-1276 microRNA, human
  • MicroRNAs
  • Mitochondrial Proteins
  • RNA, Circular
  • Metalloendopeptidases
  • molecule metalloprotease-related protein-1, human
  • SIRT4 protein, human
  • Sirtuins