Breast cancer (BC), as the most widely recognized disease in women worldwide, represents about 30% of all cancers impacting women. This study was aimed to synthesize Cu2O nanoparticles from the cystoseira myrica algae (CM-Cu2O NPs) assess their antimicrobial activity against pathogenic bacteria and fungi. We evaluated the expression levels of lncRNAs (MALAT1 and GAS5) and apoptosis genes (p53, p27, bax, bcl2 and caspase3), their prognostic roles. In this study, CM-Cu2O NPs synthesized by cystoseira myrica algae extraction used to evaluate its cytotoxicity and apoptotic properties on MDA-MB-231, SKBR3 and T-47D BC cell lines compared to HDF control cell line. The CM-Cu2O NPs was characterized by UV–Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). The antimicrobial activity of CM-Cu2O NPs was assessed against pathogenic bacteria, staphylococcus aureus (S. aureus) PTCC 1112 bacteria as a standard gram-positive bacteria and pseudomonas aeruginosa (P. aeruginosa) PTCC 1310 as a standard gram-negative bacterium. Expression profile of MALAT1 and GAS5 lncRNAs and apoptosis genes, i.e., p27, bax, bcl2 and caspase3 genes, were calculated utilizing qRT-PCR. The changes in the expression levels were determined using the DDCT method. MALAT1 was upregulated in MDA-MB-231, SKBR3 and T-47D BC (p < 0.01), while GAS5 was downregulated in SKBR3 and T-47D cell lines tested compared with HDF control cell line (p < 0.05) was found. The results revealed that, p27, bax and caspase3 were significantly upregulated in BC cell lines as compared with normal cell line. Bcl2 expression was also significantly increased in MDA-MB-231 and T47D cell lines compared with normal cell line, but bcl2 levels were downregulated in SKBR3 cell line. Our results confirm the beneficial cytotoxic effects of green-synthesized CM-Cu2O NPs on BC cell lines. This nanoparticle decreased angiogenesis and induces apoptosis, so we conclude that CM-Cu2O NPs can be used as a supplemental drug in cancer treatments. Significantly, elevated circulating lncRNAs were demonstrated to be BC specific and could differentiate BC cell lines from the normal cell lines. It was demonstrated that lncRNAs used in this study and their expression profiles can be created as biomarkers for early diagnosis and prognosis of BC. Further studies utilizing patients would give recognizable identification of lncRNAs as key players in intercellular interactions.

中文翻译：

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藻类修饰的氧化亚铜（Cu ₂ O）纳米颗粒的途径：MALAT1和GAS5 LncRNA的差异表达谱以及对人乳腺癌的细胞毒性作用

乳腺癌（BC）是全世界女性中最广泛认可的疾病，约占影响女性的所有癌症的30％。这项研究的目的是从杨梅半胱氨酸藻（CM-Cu2O NPs）合成Cu2O纳米颗粒，评估其对病原细菌和真菌的抗菌活性。我们评估了lncRNAs（MALAT1和GAS5）和凋亡基因（p53，p27，bax，bcl2和caspase3）的表达水平，及其预后作用。在这项研究中，与高密度脂蛋白（HFF）对照细胞系相比，用金丝孢半胱氨酸藻提取物合成的CM-Cu2O NPs可评估其对MDA-MB-231，SKBR3和T-47D BC细胞系的细胞毒性和凋亡特性。CM-Cu2O NPs的特征在于紫外可见光谱，傅立叶变换红外光谱（FTIR），X射线衍射（XRD），透射电子显微镜（TEM）和扫描电子显微镜（SEM）。评估了CM-Cu2O NPs对致病菌，金黄色葡萄球菌（S. aureus）PTCC 1112细菌作为标准革兰氏阳性细菌和铜绿假单胞菌（P. aeruginosa）PTCC 1310作为标准革兰氏阴性细菌的抗菌活性。利用qRT-PCR计算了MALAT1和GAS5 lncRNA的表达谱以及凋亡基因，即p27，bax，bcl2和caspase3基因。使用DDCT方法确定表达水平的变化。MALAT1在MDA-MB-231，SKBR3和T-47D BC中上调（p <0.01），而GAS5在SKBR3和T-47D细胞系中被下调（与HDF对照细胞系相比）（p <0.05）。结果表明，p27，与正常细胞系相比，BC细胞系中的bax和caspase3明显上调。与正常细胞系相比，MDA-MB-231和T47D细胞系中Bcl2表达也显着增加，但SKBR3细胞系中bcl2水平下调。我们的结果证实了绿色合成的CM-Cu2O NP对BC细胞系的有益细胞毒性作用。这种纳米颗粒减少了血管生成并诱导了细胞凋亡，因此我们得出结论，CM-Cu2O NPs可以用作癌症治疗中的补充药物。值得注意的是，升高的循环lncRNAs被证明是BC特异的，并且可以将BC细胞系与正常细胞系区分开。事实证明，这项研究中使用的lncRNA及其表达谱可以作为生物标志物用于BC的早期诊断和预后。