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探究 - 查尔酮的治疗潜力:调节 MCF-7 细胞中与乳腺癌进展相关的 microRNAs。

Exploring the Therapeutic Potential of -Chalcone: Modulation of MicroRNAs Linked to Breast Cancer Progression in MCF-7 Cells.

机构信息

Biotechnology Unit, University of Ribeirão Preto, SP, Av. Costábile Romano, 2201, Ribeirão Preto 14096-900, Brazil.

Molecular Oncology Research Center, Barretos Cancer Hospital, Teaching and Research Institute, Barretos 14784-400, Brazil.

出版信息

Int J Mol Sci. 2023 Jun 28;24(13):10785. doi: 10.3390/ijms241310785.

DOI:10.3390/ijms241310785
PMID:37445965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10341840/
Abstract

Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is -chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the -chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18 μM, respectively. Subsequently, we treated MCF-7 cells with -chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy.

摘要

乳腺癌占所有女性癌症的 25%。由于其在临床诊断中的高度异质性模式及其分子谱的差异,研究人员一直在寻找新的靶点和治疗方法,这些方法具有更高的特异性和更少的副作用。因此,一种引起我们注意的化合物是查耳酮,它天然存在于各种植物中,具有有前途的生物学特性,包括抗肿瘤作用。miRNA 是一类广泛存在的非编码小分子、内源性、单链 RNA,它参与翻译后基因调控。因此,本研究的目的是研究 TChal 对 miRNA 表达的影响及其与 MCF-7 抗癌活性的关系。首先,通过 MTT 法测定 MCF-7 和 HaCat(非癌细胞)中查耳酮的 IC50 值,发现其分别为 53.73 和 44.18 μM。随后,我们用查耳酮在其 IC50 浓度下处理 MCF-7 细胞,并进行 Mi-seq 分析,揭示了 23 个差异表达的 miRNA。在这一组中,我们选择了五个 miRNA(miR-25-5p、miR-27a-3p、miR-891a、miR-449a 和 miR-4485)进行进一步的 qRT-PCR 验证,这是基于计算机分析和它们与肿瘤发生的已知关联。总之,我们的研究为 TChal 的潜在用途提供了有价值的见解,以揭示可应用于乳腺癌治疗的 MicroRNAs 分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6df/10341840/b43eca3b0893/ijms-24-10785-g006.jpg
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