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微小RNA-376c-3p通过靶向RAB2A调节乳腺癌干细胞的特性。

miR-376c-3p modulates the properties of breast cancer stem cells by targeting RAB2A.

作者信息

Zhao Feng, Zhong Ming, Pei Wenjiang, Tian Baoxing, Cai Yantao

机构信息

Department of General Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.

出版信息

Exp Ther Med. 2020 Nov;20(5):68. doi: 10.3892/etm.2020.9196. Epub 2020 Sep 9.

Abstract

MicroRNAs (miRNAs/miRs) negatively regulate gene expression and participate in various cellular processes. miRNA dysregulation is associated with cancer progression. The present study aimed to identify the miRNAs that participate in breast cancer tumorigenesis and determine the mechanism that underlies this. miRNA microarray data analysis and validation assays indicated that miR-376c-3p was downregulated in breast tumour tissues and breast cancer stem cells (BCSCs) compared with adjacent non-cancerous tissues and MCF-10A cells, respectively. Ras-related protein Rab-2A (RAB2A) was predicted as a target of miR-376c-3p, which was confirmed by conducting further experiments. miR-376c-3p regulated the BCSC population and the expression of stem cell regulatory genes by targeting RAB2A. By performing mammosphere, Cell Counting Kit-8, colony formation and transwell invasion assays, it was demonstrated that miR-376c-3p also inhibited BCSC self-renewal, proliferation and invasion by regulating RAB2A expression. Using a xenograft mouse model, it was revealed that miR-376c-3p overexpression suppressed breast cancer growth . In conclusion, the results indicated that miR-376c-3p targeted RAB2A to regulate BCSC fate and properties; therefore, miR-376c-3p may serve as a potential therapeutic target for breast cancer.

摘要

微小RNA(miRNA/miR)负向调节基因表达并参与各种细胞过程。miRNA失调与癌症进展相关。本研究旨在鉴定参与乳腺癌肿瘤发生的miRNA,并确定其潜在机制。miRNA微阵列数据分析和验证试验表明,与相邻非癌组织和MCF-10A细胞相比,miR-376c-3p在乳腺肿瘤组织和乳腺癌干细胞(BCSC)中分别下调。Ras相关蛋白Rab-2A(RAB2A)被预测为miR-376c-3p的靶标,进一步实验证实了这一点。miR-376c-3p通过靶向RAB2A调节BCSC群体和干细胞调节基因的表达。通过进行乳腺球、细胞计数试剂盒-8、集落形成和transwell侵袭试验,证明miR-376c-3p还通过调节RAB2A表达抑制BCSC自我更新、增殖和侵袭。使用异种移植小鼠模型,发现miR-376c-3p过表达抑制乳腺癌生长。总之,结果表明miR-376c-3p靶向RAB2A调节BCSC命运和特性;因此,miR-376c-3p可能作为乳腺癌的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04cd/7490793/760257f6912b/etm-20-05-09196-g00.jpg

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