关键词: HDL breast cancer inflammation microRNA plasma lipids

Mesh : Humans Female Breast Neoplasms / genetics Interleukin-6 MicroRNAs / genetics Anti-Inflammatory Agents / pharmacology Inflammation / genetics Lipoproteins, HDL Tumor Necrosis Factor-alpha

来  源:   DOI:10.3390/ijms241612762   PDF(Pubmed)

Abstract:
The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.
摘要:
与高密度脂蛋白(HDLs)结合的炎症相关miRs的表达,从乳腺癌患者中分离出的HDLs的抗炎活性,并确定了对照。包括40名新诊断为未接受治疗的乳腺癌妇女和10名对照参与者。将负载胆固醇的骨髓来源的巨噬细胞与来自两组的HDL一起孵育,并用脂多糖(LPS)攻击。定量培养基中的白细胞介素6(IL6)和肿瘤坏死因子(TNF)。通过RT-qPCR测定HDLs中的miR。年龄,身体质量指数,更年期状态,血浆脂质,两组间HDL组成相似。与对照组相比,乳腺癌中HDL抑制IL6和TNF产生的能力更高,尤其是在疾病的晚期。与肿瘤的组织学类型无关,miR-223-3p和375-3p在乳腺癌的HDLs中更高,并且在乳腺癌和对照组之间具有很高的辨别能力。miR-375-3p在疾病的晚期阶段更高,并且与炎性细胞因子的分泌成反比。炎症相关miRs和HDLs的抗炎作用可能对乳腺癌的病理生理有重要影响。
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