PO.MCB10.01 · 分子与细胞生物学
褪黑素调控乳腺癌分子亚型中mir-340-5p表达：对亚型特异性调控和治疗靶向的意义
Melatonin modulates mir-340-5p expression in breast cancer molecular subtypes: Implications for subtype-specific regulation and therapeutic targeting
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摘要 Abstract
中文摘要
背景：乳腺癌（BC）由高度异质性的亚型组成，具有不同的分子和临床特征。三阴性乳腺癌（TNBC）以预后不良和治疗选择有限为特征，而luminal A肿瘤表现出激素受体阳性和更有利的结局。新出现的证据表明，褪黑素（MEL）通过调控基因表达（包括调控关键致癌通路的microRNA（miRNA））发挥抑癌作用。其中，miR-340-5p已被认为参与肿瘤抑制和上皮-间质转化（EMT）的调控。然而，MEL对不同BC分子亚型中该miRNA的调控仍知之甚少。因此，我们研究了褪黑素处理后代表不同分子特征（luminal A和TN）的BC细胞系中miR-340-5p的差异表达。
方法：培养人BC细胞系MCF-7和T47D（luminal A）以及MDA-MB-231（TN），不处理（对照）或用3000 μM MEL处理。使用mirVana™ miRNA分离试剂盒提取总RNA。使用High-Capacity cDNA逆转录试剂盒进行cDNA合成，并使用特异性TaqMan®试剂通过qRT-PCR定量miR-340-5p表达。使用ExpressionSuite™软件v1.3进行相对表达水平、内源性对照归一化和数据处理。
结果：与未处理对照相比，MEL处理导致MDA-MB-231（TN）细胞中miR-340-5p上调。相反，luminal A细胞系（MCF-7和T47D）在MEL处理后相对于对照细胞显示miR-340-5p表达降低。
结论：褪黑素以分子亚型依赖性方式调控miR-340-5p表达，在TN细胞中增加其表达，而在luminal A细胞中降低其表达。这种差异性调控凸显了miR-340-5p作为对褪黑素亚型特异性反应生物标志物的潜力，并可能有助于区分侵袭性与激素反应性BC表型。需要更多研究以鉴定下游靶点并阐明该调控通路的生物学意义。
查看英文原文 English abstract
Background: Breast cancer (BC) comprises highly heterogeneous subtypes with distinct molecular and clinical features. Triple-negative breast cancer (TNBC) is characterized by poor prognosis and limited therapeutic options, whereas luminal A tumors exhibit hormone receptor positivity and more favorable outcomes. Emerging evidence suggests that melatonin (MEL) exerts oncostatic effects through the modulation of gene expression, including microRNAs (miRNAs), which regulate key oncogenic pathways. Among these, miR-340-5p has been implicated in tumor suppression and in the regulation of epithelial-mesenchymal transition (EMT). However, its modulation by MEL across BC molecular subtypes remains poorly understood. Therefore, we investigated the differential expression of miR-340-5p in BC cell lines representing distinct molecular profiles (luminal A and TN) following melatonin treatment.
Methods: Human BC cell lines MCF-7 and T47D (luminal A) and MDA-MB-231 (TN) were cultured and either left untreated (control) or treated with 3000 μM MEL. Total RNA was extracted using the mirVana™ miRNA Isolation Kit. cDNA synthesis was performed with the High-Capacity cDNA Reverse Transcription Kit, and miR-340-5p expression was quantified by qRT-PCR using specific TaqMan® assays. Relative expression levels, endogenous control normalization, and data processing were performed using ExpressionSuite™ Software v1.3.
Results: MEL treatment resulted in an upregulation of miR-340-5p in MDA-MB-231 (TN) cells compared with untreated controls. Conversely, luminal A cell lines (MCF-7 and T47D) exhibited a reduction in miR-340-5p expression following MEL treatment relative to control cells.
Conclusion: Melatonin modulates miR-340-5p expression in a molecular subtype-dependent manner, increasing its expression in TN cells while reducing it in luminal A cells. This differential regulation highlights the potential of miR-340-5p as a biomarker for subtype-specific responses to melatonin and may contribute to distinguishing aggressive from hormone-responsive BC phenotypes. Additional studies are needed to identify downstream targets and elucidate the biological significance of this regulatory pathway.
利益披露 Disclosure
K. C. Carvalho, None.