circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response

Yi Tung Chen, Ian Yi Feng Chang, Chia Hua Kan, Yu Hao Liu, Yu Ping Kuo, Hsin Hao Tseng, Hsing Chun Chen, Hsuan Liu, Yu Sun Chang, Jau Song Yu, Kai Ping Chang, Bertrand Chin Ming Tan

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

Deep sequencing technologies have revealed the once uncharted non-coding transcriptome of circular RNAs (circRNAs). Despite the lack of protein-coding potential, these unorthodox yet highly stable RNA species are known to act as critical gene regulatory hubs, particularly in malignancies. However, their mechanistic implications in tumor outcome and translational potential have not been fully resolved. Using RNA-seq data, we profiled the circRNAomes of tumor specimens derived from oral squamous cell carcinoma (OSCC), which is a prevalently diagnosed cancer with a persistently low survival rate. We further catalogued dysregulated circRNAs in connection with tumorigenic progression. Using comprehensive bioinformatics analyses focused on co-expression maps and miRNA-interaction networks, we delineated the regulatory networks that are centered on circRNAs. Interestingly, we identified a tumor-associated, pro-tumorigenic circRNA, named circFLNB, that was implicated in maintaining several tumor-associated phenotypes in vitro and in vivo. Correspondingly, transcriptome profiling of circFLNB-knockdown cells showed alterations in tumor-related genes. Integrated in silico analyses further deciphered the circFLNB-targeted gene network. Together, our current study demarcates the OSCC-associated circRNAome, and unveils a novel circRNA circuit with functional implication in OSCC progression. These systems-based findings broaden mechanistic understanding of oral malignancies and raise new prospects for translational medicine.

Original languageEnglish
Article number1860
JournalCells
Volume9
Issue number8
DOIs
StatePublished - 10 08 2020

Keywords

  • biomarkers
  • circular RNA
  • miRNA–mRNA network
  • non-coding RNA
  • oral cancer

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