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Exosomes: key players in cancer and potential therapeutic strategy.外泌体:癌症中的关键角色和潜在的治疗策略。
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沉默RAB27a抑制三阴性乳腺癌细胞的增殖、侵袭和黏附

[Silencing RAB27a inhibits proliferation, invasion and adhesion of triple-negative breast cancer cells].

作者信息

Wang L, Yan Z, Xia Y

机构信息

Department of Radiation Oncology, Yunnan Provincial Cancer Hospital (Third Affiliated Hospital of Kunming Medical University), Kunming 650118, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2023 Apr 20;43(4):560-567. doi: 10.12122/j.issn.1673-4254.2023.04.08.

DOI:10.12122/j.issn.1673-4254.2023.04.08
PMID:37202191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10202786/
Abstract

OBJECTIVE

To investigate the effect of inhibition of RAB27 protein family, which plays a pivotal role in exosome secretion, on biological behaviors of triple-negative breast cancer cells.

METHODS

Quantitative real-time PCR and Western blotting were used to examine the expressions of RAB27 family and exosome secretion in 3 triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and Hs578T) and a normal breast epithelial cell line (MCF10A). The effect of small interfering RNA (siRNA)-mediated silencing of RAB27a and RAB27b on exosome secretion in the 3 breast cancer cell lines was detected using Western blotting, and the changes in cell proliferation, invasion and adhesion were evaluated.

RESULTS

Compared with normal breast epithelial cells, the 3 triple-negative breast cancer cell lines exhibited more active exosome secretion ( < 0.001) and showed significantly higher expressions of RAB27a and RAB27b at both the mRNA and protein levels ( < 0.01). Silencing of RAB27a in the breast cancer cells significantly down-regulated exosome secretion ( < 0.001), while silencing of RAB27b did not significantly affect exosome secretion. The 3 breast cancer cell lines with RAB27a silencing-induced down-regulation of exosome secretion showed obvious inhibition of proliferation, invasion and adhesion ( < 0.01) as compared with the cell lines with RAB27b silencing.

CONCLUSION

RAB27a plays central role in the exosome secretion in triple-negative breast cancer cells, and inhibiting RAB27a can inhibit the proliferation, invasion and adhesion of the cells.

摘要

目的

研究在细胞外泌体分泌中起关键作用的RAB27蛋白家族的抑制对三阴性乳腺癌细胞生物学行为的影响。

方法

采用定量实时聚合酶链反应和蛋白质免疫印迹法检测3种三阴性乳腺癌细胞系(MDA-MB-231、MDA-MB-468和Hs578T)及1种正常乳腺上皮细胞系(MCF10A)中RAB27家族的表达及细胞外泌体分泌情况。利用蛋白质免疫印迹法检测小干扰RNA介导的RAB27a和RAB27b沉默对3种乳腺癌细胞系细胞外泌体分泌的影响,并评估细胞增殖、侵袭和黏附的变化。

结果

与正常乳腺上皮细胞相比,3种三阴性乳腺癌细胞系表现出更活跃的细胞外泌体分泌(<0.001),且在mRNA和蛋白质水平上RAB27a和RAB27b的表达均显著更高(<0.01)。乳腺癌细胞中RAB27a的沉默显著下调了细胞外泌体分泌(<0.001),而RAB27b的沉默对细胞外泌体分泌无显著影响。与RAB27b沉默的细胞系相比,3种因RAB27a沉默导致细胞外泌体分泌下调的乳腺癌细胞系在增殖、侵袭和黏附方面均表现出明显抑制(<0.01)。

结论

RAB27a在三阴性乳腺癌细胞的细胞外泌体分泌中起核心作用,抑制RAB27a可抑制细胞的增殖、侵袭和黏附。