MiR-375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion

Cancer Med. 2017 Jul;6(7):1686-1697. doi: 10.1002/cam4.1110. Epub 2017 Jun 19.

Abstract

We aimed to detect the functions of miR-375/SLC7A11 axis on oral squamous cell carcinoma (OSCC) cell proliferation and invasion. Expression levels of miR-375 and SLC7A11 in OSCC tissues and cells were measured with RT-qPCR and western blot. Targeting site was predicted by TargetScan and confirmed by dual luciferase reporting assay. By way of manipulating the expression level of miR-375 and SLC7A11 in CAL-27 and Tca8113 cell lines, the cell biological abilities were evaluated. MTT, colony formation, Transwell, wound healing assays and flow cytometry were used to detect OSCC cell viability, proliferation, invasion, migration and apoptosis, respectively. MiR-375 was significantly downregulated in OSCC tissues and cells compared to adjacent tissue and normal oral cell line respectively while SLC7A11 was upregulated. Targeting relationship was verified by luciferase reporting assay, and miR-375 could effectively suppress SLC7A11 level in OSCC cells. Replenishing of miR-375 significantly repressed OSCC cell viability, proliferation, invasion and migration and induced cell apoptosis and G1/G0 arrest. Overexpression of SLC7A11 recovered those biological abilities in miR-375 upregulated cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating SLC7A11. Replenishing of miR-375 or knockout of SLC7A11 could be therapeutically exploited.

Keywords: OSCC; SLC7A11; miR-375.

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Transport System y+ / genetics*
  • Apoptosis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Mitosis / genetics
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • RNA Interference*

Substances

  • 3' Untranslated Regions
  • Amino Acid Transport System y+
  • MIRN375 microRNA, human
  • MicroRNAs
  • SLC7A11 protein, human