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Emerging role and clinical implication of mRNA scavenger decapping enzyme in colorectal cancer
Jönköping University, School of Health and Welfare, HHJ, Department of Clinical Diagnostics.ORCID iD: 0000-0003-2328-7334
Department of Laboratory Medicine and Pathology, Region Jönköping County, Jönköping, Sweden.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Department of Surgery, Region Jönköping County, Jönköping, Sweden; Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
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2023 (English)In: Pathology, Research and Practice, ISSN 0344-0338, E-ISSN 1618-0631, Vol. 253, article id 155009Article in journal (Refereed) Published
Sustainable development
00. Sustainable Development, 3. Good health and well-being
Abstract [en]

BACKGROUND: Turnover of RNA is a regulated process that in part controls gene expression. This process is partly controlled by the scavenger decapping enzyme (DcpS). This study aimed to investigate the expression of DcpS in colorectal cancer (CRC) tissue, to evaluate its prognostic significance in patients with CRC and to investigate potentially targeted genes by DcpS.

METHODS: Immunohistochemical analysis was used to determine localization of DcpS in normal and CRC tissue, western blot analysis for quantification of protein expression and qPCR for mRNA expression in normal and CRC tissue and expression in cell lines after silencing using siRNA. Gene array analysis was used to study regulation of genes after silencing of DcpS. Proliferation was studied using BRDU.

RESULTS: DcpS expression was localized to the epithelial cells of both control and cancer tissue. Tumor and paired control tissue samples from 100 patients who underwent surgical resection for primary colorectal adenocarcinomas were utilized. mRNA and protein of DcpS was significantly up-regulated in the patients with CRC and the mRNA level was higher in rectal cancer tissue compared to colon cancer tissue (p < 0.05). Lowest tertile levels of DcpS mRNA in cancer tissue was associated with a decreased cancer-specific survival rate with a hazard ratio (HR) of 4.7 (95% CI=1.02-12.3), independent of disease stage. The low level of DcpS mRNA was a predictor of poorer survival in patients with rectal and disseminated cancer and in patients receiving adjuvant treatment (p < 0.05). After silencing DcpS in Caco-2 cancer cells, altered expression of several genes associated with RNA, cell cycle regulation, alternative splicing and microRNA was observed and resulted in 23% increase in proliferation.

CONCLUSIONS: These results indicate that DcpS has potential as a prognostic factor for CRC but further studies in a broader cohort are warranted to evaluate the significance of the findings in the clinic.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 253, article id 155009
Keywords [en]
Biomarker, Cancer specific survival, Pathways, Prognostic factor, Silencing
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:hj:diva-63214DOI: 10.1016/j.prp.2023.155009ISI: 001138946600001PubMedID: 38064867Scopus ID: 2-s2.0-85179166290Local ID: HOA;;924788OAI: oai:DiVA.org:hj-63214DiVA, id: diva2:1824859
Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-29Bibliographically approved

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