MicroRNA-101 inhibits cell progression and increases paclitaxel sensitivity by suppressing MCL-1 expression in human triple-negative breast cancer.
MicroRNA-101 inhibits cell progression and increases paclitaxel sensitivity by suppressing MCL-1 expression in human triple-negative breast cancer.
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MicroRNA-101 通过抑制人三阴性乳腺癌中 MCL-1 的表达来抑制细胞进展并增加紫杉醇敏感性
DOI：
10.18632/oncotarget.4039
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发表时间：
2015-08-21
期刊：
影响因子：
--
通讯作者：
Xie X
中科院分区：
文献类型：
--
作者：
Liu X;Tang H;Chen J;Song C;Yang L;Liu P;Wang N;Xie X;Lin X;Xie X
三阴性乳腺癌是最具侵袭性的乳腺癌亚型。我们的研究目的是探讨miR-101和MCL-1在人类三阴性乳腺癌（TNBC）对紫杉醇的敏感性中的功能作用。我们发现miR-101在三阴性乳腺癌组织和细胞系中的表达明显降低。miR-101的表达与TNBC的临床分期或淋巴结浸润无关。异位过表达miR-101在体外抑制生长和诱导细胞凋亡，在体内抑制致瘤性。MCL-1在大多数TNBC组织和细胞系中显著过表达。荧光素酶检测结果证实MCL-1是miR-101的直接靶基因。MiR-101抑制TNBC细胞和移植肿瘤中MCL-1的表达。TNBC组织中miR-101与MCL-1的表达水平呈负相关。MCL-1的抑制增强了MDA-MB-435细胞对紫杉醇的敏感性。此外，miR-101通过抑制MCL-1表达增加紫杉醇敏感性。我们的研究结果为TNBC癌变的分子机制提供了重要的见解，并可能对开发针对TNBC的新型靶向治疗具有临床意义。
Triple-negative breast cancer is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of both miR-101 and MCL-1 in the sensitivity of human triple-negative breast cancer (TNBC) to paclitaxel. We found that the expression of miR-101 was strongly decreased in triple-negative breast cancer tissues and cell lines. The expression of miR-101 was not associated with clinical stage or lymph node infiltration in TNBC. Ectopic overexpression of miR-101 inhibit growth and induced apoptosis in vitro and suppressed tumorigenicity in vivo. MCL-1 was significantly overexpressed in most of the TNBC tissues and cell lines. Luciferase assay results confirmed MCL-1 as a direct target gene of miR-101. MiR-101 inhibited MCL-1 expression in TNBC cells and transplanted tumors. There was a negative correlation between the level of expression of miR-101 and MCL-1 in TNBC tissues. Suppression of MCL-1 enhanced the sensitivity of MDA-MB-435 cells to paclitaxel. Furthermore, miR-101 increased paclitaxel sensitivity by inhibiting MCL-1 expression. Our findings provide significant insight into the molecular mechanisms of TNBC carcinogenesis and may have clinical relevance for the development of novel, targeted therapies for TNBC.