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

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, t...

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Autores principales: Chen, Yi-Tung, Chang, Ian Yi-Feng, Kan, Chia-Hua, Liu, Yu-Hao, Kuo, Yu-Ping, Tseng, Hsin-Hao, Chen, Hsing-Chun, Liu, Hsuan, Chang, Yu-Sun, Yu, Jau-Song, Chang, Kai-Ping, Tan, Bertrand Chin-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464896/
https://www.ncbi.nlm.nih.gov/pubmed/32785098
http://dx.doi.org/10.3390/cells9081868
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author Chen, Yi-Tung
Chang, Ian Yi-Feng
Kan, Chia-Hua
Liu, Yu-Hao
Kuo, Yu-Ping
Tseng, Hsin-Hao
Chen, Hsing-Chun
Liu, Hsuan
Chang, Yu-Sun
Yu, Jau-Song
Chang, Kai-Ping
Tan, Bertrand Chin-Ming
author_facet Chen, Yi-Tung
Chang, Ian Yi-Feng
Kan, Chia-Hua
Liu, Yu-Hao
Kuo, Yu-Ping
Tseng, Hsin-Hao
Chen, Hsing-Chun
Liu, Hsuan
Chang, Yu-Sun
Yu, Jau-Song
Chang, Kai-Ping
Tan, Bertrand Chin-Ming
author_sort Chen, Yi-Tung
collection PubMed
description 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.
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spelling pubmed-74648962020-09-04 circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response Chen, Yi-Tung Chang, Ian Yi-Feng Kan, Chia-Hua Liu, Yu-Hao Kuo, Yu-Ping Tseng, Hsin-Hao Chen, Hsing-Chun Liu, Hsuan Chang, Yu-Sun Yu, Jau-Song Chang, Kai-Ping Tan, Bertrand Chin-Ming Cells Article 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. MDPI 2020-08-10 /pmc/articles/PMC7464896/ /pubmed/32785098 http://dx.doi.org/10.3390/cells9081868 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Yi-Tung
Chang, Ian Yi-Feng
Kan, Chia-Hua
Liu, Yu-Hao
Kuo, Yu-Ping
Tseng, Hsin-Hao
Chen, Hsing-Chun
Liu, Hsuan
Chang, Yu-Sun
Yu, Jau-Song
Chang, Kai-Ping
Tan, Bertrand Chin-Ming
circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title_full circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title_fullStr circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title_full_unstemmed circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title_short circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response
title_sort circrnaome profiling in oral carcinoma unveils a novel circflnb that mediates tumour growth-regulating transcriptional response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464896/
https://www.ncbi.nlm.nih.gov/pubmed/32785098
http://dx.doi.org/10.3390/cells9081868
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