دورية أكاديمية
أعرض في EDS

Lymphocyte antigen 6G6D-mediated modulation through p38α MAPK and DNA methylation in colorectal cancer.

التفاصيل البيبلوغرافية
العنوان: Lymphocyte antigen 6G6D-mediated modulation through p38α MAPK and DNA methylation in colorectal cancer.
المؤلفون: Caruso FP; Bioinformatics Laboratory, BIOGEM scrl, Ariano Irpino, Avellino, Italy., D'Andrea MR; UOSD Oncologia, Ospedale S. Paolo, 00053, Civitavecchia, Italy., Coppola L; UOC Anatomia ed Istologia Patologica e Citologia Diagnostica, Dipartimento dei Servizi Diagnostici e della Farmaceutica, Ospedale Sandro Pertini, ASL Roma 2, 00157, Rome, Italy., Landriscina M; Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata (CROB), Rionero in Vulture, Potenza, Italy., Condelli V; Laboratory of Pre-Clinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata (CROB), Rionero in Vulture, Potenza, Italy., Cerulo L; Bioinformatics Laboratory, BIOGEM scrl, Ariano Irpino, Avellino, Italy., Giordano G; Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122, Foggia, Italy. guido.giordano@unifg.it., Porras A; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University Madrid, 28040, Madrid, Spain. maporras@ucm.es.; Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain. maporras@ucm.es., Pancione M; Department of Sciences and Technologies, University of Sannio, Benevento, Italy. massimo.pancione@unisannio.it.
المصدر: Cancer cell international [Cancer Cell Int] 2022 Aug 11; Vol. 22 (1), pp. 253. Date of Electronic Publication: 2022 Aug 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101139795 Publication Model: Electronic Cited Medium: Print ISSN: 1475-2867 (Print) Linking ISSN: 14752867 NLM ISO Abbreviation: Cancer Cell Int Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2001-
مستخلص: In addition to being novel biomarkers for poor cancer prognosis, members of Lymphocyte antigen-6 (Ly6) gene family also play a crucial role in avoiding immune responses to tumors. However, it has not been possible to identify the underlying mechanism of how Ly6 gene regulation operates in human cancers. Transcriptome, epigenome and proteomic data from independent cancer databases were analyzed in silico and validated independently in 334 colorectal cancer tissues (CRC). RNA mediated gene silencing of regulatory genes, and treatment with MEK and p38 MAPK inhibitors were also tested in vitro. We report here that the Lymphocyte antigen 6G6D is universally downregulated in mucinous CRC, while its activation progresses through the classical adenoma-carcinoma sequence. The DNA methylation changes in LY6G6D promoter are intimately related to its transcript regulation, epigenomic and histological subtypes. Depletion of DNA methyltransferase 1 (DNMT1), which maintains DNA methylation, results in the derepression of LY6G6D expression. RNA-mediated gene silencing of p38α MAPK or its selective chemical inhibition, however, reduces LY6G6D expression, reducing trametinib's anti-inflammatory effects. Patients treated with FOLFOX-based first-line therapy experienced decreased survival due to hypermethylation of the LY6G6D promoter and decreased p38α MAPK signaling. We found that cancer-specific immunodominant epitopes are controlled by p38α MAPKs signaling and suppressed by DNA methylation in histological variants with Mucinous differentiation. This work provides a promising prospective for clinical application in diagnosis and personalized therapeutic strategies of colorectal cancer.
(© 2022. The Author(s).)
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معلومات مُعتمدة: n.4982 MIUR "FFABR"
فهرسة مساهمة: Keywords: Anti-tumor immunity; Colorectal cancer; DNA methylation; Lymphocyte antigen 6G6D
تواريخ الأحداث: Date Created: 20220811 Latest Revision: 20220815
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9373545
DOI: 10.1186/s12935-022-02672-1
PMID: 35953834
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2867
DOI:10.1186/s12935-022-02672-1