Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.
Downregulation of miR-106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2.
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miR-106b 的下调诱导乳腺癌细胞侵袭和运动，与基质金属蛋白酶 2 的过度表达相关
DOI：
10.1111/cas.12309
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发表时间：
2014-01
期刊：
影响因子：
5.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Ni X;Xia T;Zhao Y;Zhou W;Wu N;Liu X;Ding Q;Zha X;Sha J;Wang S
乳腺癌(BC)是女性最常见的癌症之一，通常会转移到骨骼。BC骨转移的机制尚不清楚，需要深入研究。在先前的研究中，我们发现基质金属蛋白酶2(MMP2)在转移性骨组织中的表达明显高于原位骨组织。MicroRNA表达谱显示miR-106b在BC骨转移过程中显著下调。然而，MMP2和miR-106b参与BC骨转移的具体机制尚不清楚。在目前的研究中，我们发现MMP2在原位肿瘤组织中的表达与BC患者骨转移的风险有关。原位肿瘤组织中MIR-106b水平与MMP2表达和乳腺癌骨转移呈负相关。MMP2被证明是miR-106b的直接靶点。功能获得和功能丧失研究均表明，MMP2可促进BC细胞的迁移和侵袭，而miR-106b可抑制两者。RNA干扰阻断MMP2可模拟miR-106b的抗迁移和抗侵袭作用，MMP2的引入可拮抗miR-106b的作用。MMP2也被发现调节ERK信号转导通路，从而调节骨微环境，有利于破骨细胞的形成和骨转移。提示MMP2表达上调通过ERK途径在BC骨转移中起重要作用，miR-106b直接调节MMP2的表达。MiR-106b/MMP2/ERK通路有望成为抑制BC骨转移的治疗靶点。
Breast cancer (BC) is one of the most common cancers in women, and it can often metastasize to the bone. The mechanism of BC bone metastasis remains unclear and requires in-depth investigation. In a previous study, we found the expression of matrix metalloproteinase 2 (MMP2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites. MicroRNA expression profiling showed miR-106b to be markedly downregulated during BC bone metastasis. However, the specific manner in which MMP2 and miR-106b are involved in the BC bone metastasis is still unclear. In the present study, we found MMP2 expression in orthotopic tumor tissue to be related to the risk of bone metastasis in BC patients. MiR-106b levels in orthotopic tumor tissue showed a negative correlation with MMP2 expression and breast cancer bone metastasis. MMP2 was shown to be a direct target of miR-106b. Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both. The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b. MMP2 was also found to regulate the ERK signaling cascade and so adjust the bone microenvironment to favor osteoclastogenesis and bone metastasis. These results suggest that MMP2 upregulation plays an important role in BC bone metastasis through ERK pathways, and miR-106b directly regulates MMP2 expression. The miR-106b/MMP2/ERK pathway may be a promising therapeutic target for inhibiting BC bone metastasis.
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影响因子：
20.3
作者：
Sampath, Deepa;Calin, George A.;Plunkett, William
通讯作者：
Plunkett, William
影响因子：
64.5
作者：
Valastyan S;Reinhardt F;Benaich N;Calogrias D;Szász AM;Wang ZC;Brock JE;Richardson AL;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
11.5
作者：
Leppä, S;Saarto, T;Elomaa, I
通讯作者：
Elomaa, I
影响因子：
50.5
作者：
McGowan, P. M.;Duffy, M. J.
通讯作者：
Duffy, M. J.
影响因子：
3.8
作者：
Xia, Tian-Song;Wang, Guo-Zhu;Wang, Shui
通讯作者：
Wang, Shui