Low expression of miR-let-7a promotes cell growth and invasion through the regulation of c-Myc in oral squamous cell carcinoma

Cell Cycle. 2020 Aug;19(15):1983-1993. doi: 10.1080/15384101.2020.1786633. Epub 2020 Jun 28.

Abstract

In oral squamous cell carcinoma (OSCC), abnormal expression of microRNAs has been extensively reported. MiR-let-7a has been validated as a critical regulator of multiple cancers, but the biological process involved and its potential role in OSCC remain unknown.We first analyzed the differential expression of miR-let-7a in cancer tissues, adjacent noncancerous tissues and cell lines. The functional role of miR-let-7a in OSCC cell lines was evaluated by using colony formation assays, cell proliferation and transwell invasion assays in vitro. In addition, subcutaneous xenotransplantation of miR-let-7a transfected cells into nude mouse model was carried out to explore the potential function of miR-let-7a in vivo.miR-let-7a levels were found to be significantly downregulated in OSCC tissues compared with matched normal tissues (n = 60), and lower expression of miR-let-7a was related to poor prognosis in OSCC patients. Overexpression of MiR-let-7a induced a suppression in proliferation, invasion and migration and inhibited tumourigenesis in the nude mouse model. We also determined that c-Myc may serve as a direct target of miR-let-7a; furthermore, upregulated c-Myc expression could partially rescue the effects caused by miR-let-7a overexpression. miR-let-7a is low expression in OSCC, and promotes tumor development by directly targeting c-Myc. Our results may provide a potential therapeutic role for miR-let-7a in human OSCC.

Keywords: OSCC; invasion; miR-let-7a; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • mirnlet7 microRNA, human

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81672169, No. 81974332).