miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer

BMC Cancer. 2022 May 12;22(1):533. doi: 10.1186/s12885-022-09603-3.

Abstract

Background: As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC.

Methods: MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model.

Results: We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3'-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107.

Conclusions: These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.

Keywords: Breast cancer; Cancer invasion; Cancer metastasis; NEDD9; miR-107.

MeSH terms

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Neoplasm Invasiveness / genetics

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • MIRN107 microRNA, human
  • MicroRNAs
  • NEDD9 protein, human