Cargando…

A RNA-Sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer

Long non-coding RNAs (lncRNAs) have been implicated in human pathology, however, their role in colorectal carcinogenesis have not been fully elucidated. In the current study, whole-transcriptome analysis was performed in 3 pairs of colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequen...

Descripción completa

Detalles Bibliográficos
Autores principales: Yamada, Atsushi, Yu, Pingjian, Lin, Wei, Okugawa, Yoshinaga, Boland, C. Richard, Goel, Ajay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766599/
https://www.ncbi.nlm.nih.gov/pubmed/29330370
http://dx.doi.org/10.1038/s41598-017-18407-6
Descripción
Sumario:Long non-coding RNAs (lncRNAs) have been implicated in human pathology, however, their role in colorectal carcinogenesis have not been fully elucidated. In the current study, whole-transcriptome analysis was performed in 3 pairs of colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequencing (RNA-seq). Followed by confirmation using the Cancer Genome Atlas (TCGA) dataset, we identified 27 up-regulated and 22 down-regulated lncRNAs in CRC. Up-regulation of four lncRNAs, hereby named colorectal cancer associated lncRNA (CRCAL)-1 [AC021218.2], CRCAL-2 [LINC00858], CRCAL-3 [RP11-138J23.1] and CRCAL-4 [RP11-435O5.2], was further validated by real-time RT-PCR in 139 colorectal neoplasms and matched NM tissues. Knockdown of CRCAL-3 and CRCAL-4 in colon cancer cells reduced cell viability and colony formation ability, and induced cell cycle arrest. TCGA dataset supported the associations of CRCAL-3 and CRCAL-4 with cell cycle and revealed a co-expression network comprising dysregulated lncRNAs associated with protein-coding genes. In conclusion, RNA-seq identified numbers of novel lncRNAs dysregulated in CRC. In vitro experiments and GO term enrichment analysis indicated the functional relevance of CRCAL-3 and CRCAL-4 in association with cell cycle. Our data highlight the capability of RNA-seq to discover novel lncRNAs involved in human carcinogenesis, which may serve as alternative biomarkers and/or molecular treatment targets.