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- Title
Annotation and functional characterization of long noncoding RNAs deregulated in pancreatic adenocarcinoma.
- Authors
da Paixão, Vinicius Ferreira; Sosa, Omar Julio; da Silva Pellegrina, Diogo Vieira; Dazzani, Bianca; Corrêa, Thalita Bueno; Risério Bertoldi, Ester; da Cruz e Alves-de-Moraes, Luís Bruno; de Oliveira Pessoa, Diogo; de Paiva Oliveira, Victoria; Alberto Chiong Zevallos, Ricardo; Russo, Lilian Cristina; Luis Forti, Fabio; Eduardo Ferreira, João; Carioca Freitas, Helano; Jukemura, José; Machado, Marcel Cerqueira César; Dirlei Begnami, Maria; Setubal, João Carlos; Bassères, Daniela Sanchez; Moraes Reis, Eduardo
- Abstract
Purpose: Transcriptome analysis of pancreatic ductal adenocarcinoma (PDAC) has been useful to identify gene expression changes that sustain malignant phenotypes. Yet, most studies examined only tumor tissues and focused on protein-coding genes, leaving long non-coding RNAs (lncRNAs) largely underexplored. Methods: We generated total RNA-Seq data from patient-matched tumor and nonmalignant pancreatic tissues and implemented a computational pipeline to survey known and novel lncRNAs. siRNA-mediated knockdown in tumor cell lines was performed to assess the contribution of PDAC-associated lncRNAs to malignant phenotypes. Gene co-expression network and functional enrichment analyses were used to assign deregulated lncRNAs to biological processes and molecular pathways. Results: We detected 9,032 GENCODE lncRNAs as well as 523 unannotated lncRNAs, including transcripts significantly associated with patient outcome. Aberrant expression of a subset of novel and known lncRNAs was confirmed in patient samples and cell lines. siRNA-mediated knockdown of a subset of these lncRNAs (LINC01559, LINC01133, CCAT1, LINC00920 and UCA1) reduced cell proliferation, migration and invasion. Gene co-expression network analysis associated PDAC-deregulated lncRNAs with diverse biological processes, such as cell adhesion, protein glycosylation and DNA repair. Furthermore, UCA1 knockdown was shown to specifically deregulate co-expressed genes involved in DNA repair and to negatively impact DNA repair following damage induced by ionizing radiation. Conclusions: Our study expands the repertoire of lncRNAs deregulated in PDAC, thereby revealing novel candidate biomarkers for patient risk stratification. It also provides a roadmap for functional assays aimed to characterize novel mechanisms of action of lncRNAs in pancreatic cancer, which could be explored for therapeutic development.
- Subjects
LINCRNA; PANCREATIC duct; DNA repair; IONIZING radiation; ADENOCARCINOMA; GENE regulatory networks; CELL migration
- Publication
Cellular Oncology (2211-3428), 2022, Vol 45, Issue 3, p479
- ISSN
2211-3428
- Publication type
Article
- DOI
10.1007/s13402-022-00678-5