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Published on: February 19, 2022
Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs)
Ugne Gyvyte1, Juozas Kupcinskas1,2, Simonas Juzenas1,3
1Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Abstract:
Long intergenic non-coding RNAs (lincRNAs) are >200 nucleotides long non-coding RNAs, which have been shown to be implicated in carcinogenic processes by interacting with cancer associated genes or other non-coding RNAs. However, their role in development of rare gastrointestinal stromal tumors (GISTs) is barely investigated. Therefore, the aim of this study was to define lincRNAs deregulated in GIST and find new GIST-lincRNA associations. Next-generation sequencing data of paired GIST and adjacent tissue samples from 15 patients were subjected to a web-based lincRNA analysis. Three deregulated lincRNAs (MALAT1, H19 and FENDRR; adjusted p-value < 0.05) were selected for expression validation in a larger group of patients (n = 22) by RT-qPCR method. However, only H19 and FENDRR showed significant upregulation in the validation cohort (adjusted p < 0.05). Further, we performed correlation analyses between expression levels of deregulated lincRNAs and GIST-associated oncogenes or GIST deregulated microRNAs. We found high positive correlations between expression of H19 and known GIST related oncogene ETV1, and between H19 and miR-455-3p. These findings expand the knowledge on lincRNAs deregulated in GIST and may be an important resource for the future studies investigating lincRNAs functionally relevant to GIST carcinogenesis.
Insights
This study identified deregulated long intergenic non-coding RNAs (lincRNAs) in gastrointestinal stromal tumors (GIST). H19 and FENDRR were significantly upregulated, with H19 correlating with GIST oncogene ETV1 and miR-455-3p.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long intergenic non-coding RNAs (lincRNAs) are implicated in cancer but their role in gastrointestinal stromal tumors (GIST) is understudied.
- GIST is a rare cancer with limited understanding of its molecular drivers.
Purpose of the Study:
- To identify deregulated lincRNAs in GIST.
- To explore associations between lincRNAs and GIST-related genes or microRNAs.
Main Methods:
- Next-generation sequencing of paired GIST and adjacent tissues.
- Bioinformatic analysis to identify deregulated lincRNAs.
- RT-qPCR for expression validation.
- Correlation analysis with oncogenes and microRNAs.
Main Results:
- Three lincRNAs (MALAT1, H19, FENDRR) were initially identified as deregulated.
- H19 and FENDRR showed significant upregulation in GIST validation cohort.
- H19 expression positively correlated with GIST oncogene ETV1 and miR-455-3p.
Conclusions:
- H19 and FENDRR are upregulated in GIST.
- H19 may play a role in GIST development through its association with ETV1 and miR-455-3p.
- These findings provide a resource for future GIST research.
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