Abstract
BackgroundBreast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstream regulation of MEG3 in breast cancer remain elusive. Therefore, it is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis.MethodsWe employed RT-qPCR and Western blot to examine expression level of miR-506, DNMT1, SP1, SP3 and MEG3. Besides, methylation-specific PCR was used to determine the methylation level of MEG3 promoter. Wound healing assay and transwell invasion assay were utilized to measure migration and invasion ability of breast cancer cells, respectively.ResultsSP was upregulated while miR-506 and MEG3 were downregulated in breast tumor tissue compared to adjacent normal breast tissues. In addition, we found that miR-506 regulated DNMT1 expression in an SP1/SP3-dependent manner, which reduced methylation level of MEG3 promoter and upregulated MEG3 expression. SP3 knockdown or miR-506 mimic suppressed migration and invasion of MCF-7 and MDA-MB-231 cells whereas overexpression of SP3 compromised miR-506-inhibited migration and invasion.ConclusionsOur data reveal a novel axis of miR-506/SP3/SP1/DNMT1/MEG3 in regulating migration and invasion of breast cancer cell lines, which provide rationales for developing effective therapies to treating metastatic breast cancers.
Highlights
Breast cancer has been the first death cause of cancer in women all over the world
Our findings reveal the detailed mechanism by which miR-506 regulates metastasis of breast cancer, which facilitates the development of therapeutical strategies for treating breast cancer
SP3 depletion suppresses migration and invasion of breast cancer cells We firstly attempted to examine the effect of SP3 on metastasis of breast cancer
Summary
Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. Upstream regulation of MEG3 in breast cancer remain elusive. It is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis. Breast cancer is the most common cause of cancerrelated death in women worldwide [1,2,3]. Similar to other solid tumors, distant metastasis (especially lung metastasis) is the leading cause of breast cancer-associated death and resistance to various treatments [4]. Arora et al [11] reported that miR-506 had a role in regulating EMT in breast cancer cell lines. Yu et al [12] has shown that miR-506 overexpression inhibits proliferation and metastasis of breast cancer cells. The mechanism of miR-506 inhibition of breast cancer metastasis remains elusive
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