نتائج البحث - "CRC cell lines"

المساهمون: Di Donato, Marzia, Di Zazzo, Erika, Salvati, Annamaria, Sorrentino, Carmela, Giurato, Giorgio, Fiore, Donatella, Proto, MARIA CHIARA, Rienzo, Monica, Casamassimi, Amelia, Gazzerro, Patrizia, Bifulco, Maurizio, Castoria, Gabriella, Weisz, Alessandro, Nassa, Giovanni, Abbondanza, Ciro

مصطلحات موضوعية: Background: Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2). The imbalance in their expression levels in favor of RIZ2 is observed in many cancer types. The full length RIZ1 has been extensively investigated in several cancers where it acts as a tumor suppressor, whereas few studies have explored the RIZ2 oncogenic properties. PRDM2 is often target of frameshift mutations and aberrant DNA methylation in CRC. However, little is known about its role in CRC. Methods: We combined in-silico investigation of The Cancer Genome Atlas (TCGA) CRC datasets, cellular and molecular assays, transcriptome sequencing and functional annotation analysis to assess the role of RIZ2 in human CRC. Results: Our in-silico analysis on TCGA datasets confirmed that PRDM2 gene is frequently mutated and transcriptionally deregulated in CRC and revealed that a RIZ2 increase is highly correlated with a significant RIZ1 downregulation. Then, we assayed several CRC cell lines by qRT-PCR analysis for the main PRDM2 transcripts and selected DLD1 cell line, which showed the lowest RIZ2 levels. Therefore, we overexpressed RIZ2 in these cells to mimic TCGA datasets analysis results and consequently to assess the PRDM2/RIZ2 role in CRC. Data from RNA-seq disclosed that RIZ2 overexpression induced profound changes in CRC cell transcriptome via EGF pathway deregulation, suggesting that RIZ2 is involved in the EGF autocrine regulation of DLD1 cell behavior. Noteworthy, the forced RIZ2 expression increased cell viability, growth, colony formation, migration and organoid formation. These effects could be mediated by the release of high EGF levels by RIZ2 overexpressing DLD1 cells. Conclusions: Our findings add novel insights on the putative RIZ2 tumor-promoting functions in CRC, although additional efforts are warranted to define the underlying molecular mechanism.

وصف الملف: ELETTRONICO

Relation: info:eu-repo/semantics/altIdentifier/pmid/37853459; info:eu-repo/semantics/altIdentifier/wos/WOS:001099615800003; volume:21; firstpage:1; lastpage:19; numberofpages:19; journal:JOURNAL OF TRANSLATIONAL MEDICINE; https://hdl.handle.net/11386/4848651; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85174463233; https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04621-6

الاتاحة: https://hdl.handle.net/11386/4848651
https://doi.org/10.1186/s12967-023-04621-6
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04621-6

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