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微小RNA对乳腺癌中Wnt相关基因活性的影响。

Impact of MiRNAs on Wnt-related gene activity in breast cancer.

作者信息

Sirek Tomasz, Sirek Agata, Zmarzły Nikola, Opławski Marcin, Król-Jatręga Katarzyna, Boroń Dariusz, Chalcarz Michał, Ossowski Piotr, Dziobek Konrad, Strojny Damian, Szymańska Joanna, Gajdeczka Julia, Borawski Przemysław, Boroń Kacper, Grabarek Beniamin Oskar

机构信息

Department of Plastic Surgery, Faculty of Medicine, Academia of Silesia, Katowice, 40-555, Poland.

Department of Plastic and Reconstructive Surgery, Hospital for Minimally Invasive and Reconstructive Surgery in Bielsko-Biała, Bielsko-Biala, 43-316, Poland.

出版信息

Sci Rep. 2025 May 9;15(1):16211. doi: 10.1038/s41598-025-00343-5.

Abstract

Breast cancer is the most commonly diagnosed cancer in women. The Wnt pathway is involved in the regulation of cell proliferation, differentiation, survival, and migration. Its disruption may promote the induction of breast cancer and its further development. The aim of the study was to identify micro RNA (miRNAs) that could potentially influence the activity of Wnt-related genes in five types of breast cancer in Polish women. Study included patients with five breast cancer subtypes: 130 luminal A, 96 HER2-positive luminal B, 100 HER2-negative luminal B, 36 non-luminal HER2-positive, 43 triple negative breast cancer (TNBC). Tumor tissue was removed during surgery along with a margin of healthy tissue (control group). Expression profile of Wnt-related genes was assessed with mRNA microarrays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression was conducted with enzyme-linked immunosorbent assay (ELISA). miRNA profiling was carried out with miRNAs microarrays and the miRDB database. Reduced activity of miR-130a could be related to overexpression of CCND1 and GSK3B. Similarly for miR-199a and GSK3B. High activity of miR-2115 could be associated with downregulation of TCF7L2. WNT5 A overexpression may be linked to low levels of miR-497. In addition, study revealed increased levels of APC, DVL3, LEF1 with reduced activity of FZD4 and TCF7L1 in all five subtypes of breast cancer.

摘要

乳腺癌是女性中最常被诊断出的癌症。Wnt信号通路参与细胞增殖、分化、存活和迁移的调控。其破坏可能促进乳腺癌的诱发及其进一步发展。本研究的目的是鉴定可能影响波兰女性五种类型乳腺癌中Wnt相关基因活性的微小RNA(miRNA)。研究纳入了患有五种乳腺癌亚型的患者:130例腔面A型、96例HER2阳性腔面B型、100例HER2阴性腔面B型、36例非腔面HER2阳性、43例三阴性乳腺癌(TNBC)。手术期间切除肿瘤组织以及健康组织边缘(对照组)。通过mRNA微阵列和逆转录定量聚合酶链反应(RT-qPCR)评估Wnt相关基因的表达谱。采用酶联免疫吸附测定(ELISA)进行蛋白质表达检测。利用miRNA微阵列和miRDB数据库进行miRNA谱分析。miR-130a活性降低可能与CCND1和GSK3B的过表达有关。miR-199a和GSK3B情况类似。miR-2115的高活性可能与TCF7L2的下调有关。WNT5A的过表达可能与miR-497的低水平有关。此外,研究显示在所有五种乳腺癌亚型中,APC、DVL3、LEF1水平升高,而FZD4和TCF7L1活性降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dbe/12064741/fa56117a5e1b/41598_2025_343_Fig1_HTML.jpg

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