circIGHG-Induced Epithelial-to-Mesenchymal Transition Promotes Oral Squamous Cell Carcinoma Progression via miR-142-5p/IGF2BP3 Signaling

Cancer Res. 2021 Jan 15;81(2):344-355. doi: 10.1158/0008-5472.CAN-20-0554. Epub 2020 Nov 17.

Abstract

Circular RNAs (circRNA) are a new member of endogenously produced noncoding RNAs that have been characterized as key regulators of gene expression in a variety of malignances. However, the role of circRNA in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we identified unique circRNA that regulate OSCC progression and metastasis and pave roads for future research in early diagnosis, prevention, and treatment of OSCC. Transcriptomic analyses identified a circRNA derived from IGHG locus (circIGHG) as significantly upregulated in OSCC and positively associated with poor prognosis of OSCC. circIGHG directly bound miR-142-5p and consequently elevated IGF2BP3 activity. Knockdown of circIGHG led to impaired expression of IGF2BP3 and attenuated aggressiveness of OSCC cells. Epithelial-mesenchymal transition was the main mechanism through which circIGHG/IGF2BP3 promotes metastasis of OSCC. Overall, these results demonstrate that circIGHG plays a pivotal role in OSCC development and metastasis and has potential to serve as a biomarker and therapeutic target for early-stage diagnosis and treatment of OSCC. SIGNIFICANCE: These findings broaden our insights regarding regulation of OSCC progression by circular RNA and serve as a reference for future clinical research in OSCC diagnosis and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Prognosis
  • RNA, Circular / genetics*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • IGF2BP3 protein, human
  • MIRN142 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins