Promotion of tumorigenesis by miR-1260b-targeting CASP8: Potential diagnostic and prognostic marker for breast cancer

Cancer Sci. 2022 Jun;113(6):2097-2108. doi: 10.1111/cas.15345. Epub 2022 Mar 31.

Abstract

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.

Keywords: CASP8; breast cancer; diagnosis; miR-1260b; prognosis.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Carcinogenesis / genetics
  • Caspase 8* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Prognosis

Substances

  • Biomarkers, Tumor
  • MIRN1260 microRNA, human
  • MicroRNAs
  • CASP8 protein, human
  • Caspase 8