miR-5191 acts as a tumor suppressor in salivary adenoid cystic carcinoma by targeting Notch-2

Oral Dis. 2022 Oct;28(7):1871-1881. doi: 10.1111/odi.13841. Epub 2021 Apr 28.

Abstract

Objective: This study sought to investigate the effect of miR-5191 on proliferation, invasion and metastasis in salivary adenoid cystic carcinoma (SACC).

Materials and methods: The differential expression level of miR-5191 between 5 primary tumor and adjacent non-neoplastic samples, and in two SACC cell lines was detected by quantitative real-time PCR. Cell proliferation, invasion, and migration were performed, followed by luciferase reporter assay and western analysis. The effect of miR-5191 on cell proliferation and apoptosis was evaluated by cell growth and apoptosis assay. The function of miR-5191 in SACC tumorigenesis and metastasis in vivo was investigated by nude mice experiment. The associations between miR-5191/Notch-2 expression and clinicopathological features were analyzed.

Results: miR-5191 was downregulated in primary tumor tissues and SACC-LM cells. By targeting Notch-2, miR-5191 expression level affected the migration, invasion, and proliferation of SACC cells. Overexpression of miR-5191 inhibited the expression levels of Notch-2, followed by the decreased expression of c-Myc, Bcl-2, Hes-1, Hey-1, and Cyclin D1. In vivo, miR-5191 overexpression suppressed the SACC tumorigenesis and pulmonary metastasis in mice. In SACC patients, higher expression of miR-5191 was related to better prognoses and lower possibility of metastasis.

Conclusions: miR-5191 acts as a tumor suppressor in SACC by targeting Notch-2.

Keywords: Notch-2; metastasis; miR-5191; salivary adenoid cystic carcinoma.

MeSH terms

  • Animals
  • Carcinogenesis
  • Carcinoma, Adenoid Cystic* / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Receptor, Notch2 / metabolism*
  • Salivary Gland Neoplasms* / pathology

Substances

  • MicroRNAs
  • NOTCH2 protein, human
  • Receptor, Notch2