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新诊断的晚期乳腺癌女性 HDL 中 miR-223-3p 和 miR-375-3p 的表达增加和抗炎活性。

Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer.

机构信息

Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-000, Brazil.

Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo 01525-000, Brazil.

出版信息

Int J Mol Sci. 2023 Aug 14;24(16):12762. doi: 10.3390/ijms241612762.

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

测定了与高密度脂蛋白(HDL)结合的炎症相关 miR 的表达、从乳腺癌患者和对照者中分离的 HDL 的抗炎活性。纳入 40 例新诊断的未经治疗的乳腺癌女性和 10 例对照者。用来自两组的 HDL 孵育载有胆固醇的骨髓源性巨噬细胞,并用脂多糖(LPS)进行挑战。定量测定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 HDL 中的 miR。两组间的年龄、体重指数、绝经状态、血浆脂质和 HDL 组成相似。与对照组相比,乳腺癌患者的 HDL 抑制 IL6 和 TNF 产生的能力更高,尤其是在疾病的晚期。miR-223-3p 和 375-3p 在乳腺癌患者的 HDL 中更高,而与肿瘤的组织学类型无关,并且在乳腺癌和对照组之间具有很高的区分能力。miR-375-3p 在疾病的晚期更高,并且与炎症细胞因子的分泌呈负相关。炎症相关 miR 和 HDL 的抗炎作用可能对乳腺癌的病理生理学有重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bcc/10454463/88c07d5db9e1/ijms-24-12762-g001.jpg

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