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Methyltransferase 3A-mediated promoter methylation represses retinoic acid receptor responder 3 expression in basal-like breast cancer

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BIOCELL 2023年第2期47卷 319-328页

作者： YOULIN TUO XUBAO LIU Department of Pancreatic Surgery West China HospitalSichuan UniversityChengdu610041China

Retinoic acid receptor responder 3(RARRES3)has been characterized as a tumor suppressor in multiple types of *** study aimed to examine the expression profile of RARRES3 across the PAM50 subtypes of breast *** DNA methylation status of RARRES3 was checked in the basal-like subtype,and the underlying mechanisms of its dysregulation were ***-sequencing(seq)and methylation data from The cancer Genome Atlas were used for in-silico ***-like representative SUM149 and MDA-MB-468 cell lines were used for in vitro and in vivo *** to tumor-adjacent normal tissues,only the basal-like tumor tissues had significantly downregulated RARRES3 *** methylation level of four CpG sites in the promoter region showed a strong negative correlation with RARRES3 *** gene coding for DNA methyltransferase 3A(DNMT3A)had consistent positive correlations with the methylation of the CpG *** Immunoprecipitation-quantitative polymerase chain-reaction and bisulfite sequencing PCR showed that DNMT3A could bind to the promoter region of RARRES3 and promote methylation of the CpG sites within the ***3A knockdown significantly restored RARRES3 expression at the mRNA and protein level in the two cell ***-8,colony formation,and flow cytometric analysis showed that RARRES3 overexpression attenuated the growth-promoting effects of DNMT3A overexpression and also weakened the DNMT3A overexpression-induced activation of ERK1/2 and PI3K/AKT *** summary,this study revealed that DNMT3A enhances promoter methylation of the RARRES3 gene and suppresses its transcription in basal-like breast *** DNMT3A-RARRES3 signaling pathway might be a potential target for the treatment of this tumor subtype.

关键词： DNMT3A basal-like breast cancer RARRES3 Promoter methylation

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Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

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Chinese Journal of cancer Research 2017年第3期29卷 237-252页

作者： Tianjian Yu Genhong Di Department of breast Surgery Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix (ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer (TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings.

关键词： Triple-negative breast cancer basal-like breast cancer tumor microenvironment prognosis

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