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微小RNA-143靶向CD44以抑制乳腺癌进展及干细胞样特性。

MicroRNA‑143 targets CD44 to inhibit breast cancer progression and stem cell-like properties.

作者信息

Yang Zhuangqing, Chen Dedian, Nie Jianyun, Zhou Shaoqiang, Wang Jiankui, Tang Qi, Yang Xiaojuan

机构信息

Department of Mammary Glands, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, Yunnan 650118, P.R. China.

出版信息

Mol Med Rep. 2016 Jun;13(6):5193-9. doi: 10.3892/mmr.2016.5194. Epub 2016 Apr 27.

Abstract

CD44 is closely linked to breast cancer progression; however, the regulatory functions of microRNAs (miRs) in breast cancer have yet to be fully elucidated. In order to investigate the regulation of CD44 by miRs in breast cancer, the present study isolated CD44+ and CD44- breast cancer cells by flow cytometry, revealing that CD44+ cells were enriched in transplanted compared with those in primary breast cancers, and that their proliferation and stem-cell sphere formation ability were enhanced. A miRNA array assay indicated that miR-143 expression in CD44+ breast cancer cells was lower than that in CD44- cells. Furthermore, miR-143 was decreased in breast cancer tissues and cell lines compared with that in normal tissues and cells. Restoration of miR-143 expression in CD44+ breast cancer cells inhibited their proliferation and sphere formation. A luciferase reporter assay demonstrated that miR-143 directly tartgeted the 3'-untranslated region of CD44. In addition, miR-143 inhibited metastasis-associated features in breast cancer and reduced tumor growth in a mouse model of breast cancer. In conclusion, the results of the present study demonstrated that miR-143 inhibited the progression and stem-cell properties of breast cancer cells by targeting CD44.

摘要

CD44与乳腺癌进展密切相关;然而,微小RNA(miR)在乳腺癌中的调控功能尚未完全阐明。为了研究miR在乳腺癌中对CD44的调控作用,本研究通过流式细胞术分离出CD44+和CD44-乳腺癌细胞,结果显示与原发性乳腺癌相比,CD44+细胞在移植瘤中富集,且其增殖和干细胞球形成能力增强。一项miRNA阵列分析表明,CD44+乳腺癌细胞中miR-143的表达低于CD44-细胞。此外,与正常组织和细胞相比,乳腺癌组织和细胞系中miR-143表达降低。在CD44+乳腺癌细胞中恢复miR-143表达可抑制其增殖和球形成。荧光素酶报告基因检测表明,miR-143直接靶向CD44的3'-非翻译区。此外,miR-143在乳腺癌小鼠模型中抑制了转移相关特征并减少了肿瘤生长。总之,本研究结果表明,miR-143通过靶向CD44抑制乳腺癌细胞的进展和干细胞特性。

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