Open AccessDownregulation of miR‐106b induced breast cancer cell invasion and motility in association with overexpression of matrix metalloproteinase 2
Author(s) -
Ni Xiaojian,
Xia Tiansong,
Zhao Yingchun,
Zhou Wenbin,
Wu Naping,
Liu Xiaoan,
Ding Qiang,
Zha Xiaoming,
Sha Jiahao,
Wang Shui
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12309
Subject(s) - mmp2 , bone metastasis , metastasis , cancer research , downregulation and upregulation , matrix metalloproteinase , mapk/erk pathway , cell migration , tumor progression , medicine , cancer , biology , signal transduction , cell , microbiology and biotechnology , biochemistry , genetics , gene
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 ( MMP 2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites. Micro RNA expression profiling showed miR‐106b to be markedly downregulated during BC bone metastasis. However, the specific manner in which MMP 2 and miR‐106b are involved in the BC bone metastasis is still unclear. In the present study, we found MMP 2 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 MMP 2 expression and breast cancer bone metastasis. MMP 2 was shown to be a direct target of miR‐106b. Both gain‐ and loss‐of‐function studies showed that MMP 2 could promote the migration and invasion of BC cells and that miR‐106b could suppress both. The blockage of MMP 2 by RNA interference mimicked the anti‐migration and anti‐invasion effects of miR‐106b, and introduction of MMP 2 antagonized the function of miR‐106b. MMP 2 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 MMP 2 upregulation plays an important role in BC bone metastasis through ERK pathways, and miR‐106b directly regulates MMP 2 expression. The miR‐106b/ MMP 2/ ERK pathway may be a promising therapeutic target for inhibiting BC bone metastasis.