Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR (qRT-PCR). Junctional adhesion molecule A (JAM-A) was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-of-function assays, and the inhibition of JAM-A by miR-495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-495 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-014-0088-2) contains supplementary material, which is available to authorized users.
Highlights
Breast cancer is the most common malignancy and the leading cause of cancer death among females worldwide, accounting for ∼36% of female primary malignant tumors (Jemal et al, 2011)
The level of miR-495 in clinical breast cancer tissue samples was determined using quantitative real time-PCR, and we found that the level of miR-495 in breast cancer tissues was markedly higher than in paired adjacent normal breast tissues (Fig. 1A), suggesting that miR-495 is associated with the progression of breast cancer
The level of miR-495 in two different breast cancer cell lines MCF-7 and MDA-MB-231 cells was detected, and we found that miR-495 was significantly up-regulated in MDA-MB-231
Summary
Breast cancer is the most common malignancy and the leading cause of cancer death among females worldwide, accounting for ∼36% of female primary malignant tumors (Jemal et al, 2011). By base-pairing with 3′-untranslated region (3′-UTR) of messenger RNA (mRNA), miRNAs can repress the expression of target genes by inhibiting translation or by destabilizing the mRNA (Bartel, 2009; Fabian et al, 2010). With an increasing number of target genes of miRNAs being validated by experimental assays and verified in clinical samples, miRNAs have gradually emerged as a new important regulator of tumorigenesis and have been found to be involved in various aspects of cancer progression including tumor metastasis
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