Hsa-miR-1 suppresses breast cancer development by down-regulating K-ras and long non-coding RNA MALAT1
Introduction
Breast cancer is a common malignancy, with an incidence of more than 1,000,000 new cases and 370,000 deaths annually worldwide [1]. Unfortunately, most breast cancer patients tend to present a more advanced stage of disease when first diagnosed [2]. Thus, it is urgent to gain further insight into the molecular mechanism of the progression of breast cancer.
MicroRNAs (miRNAs) are small non-coding RNAs of about 22 nucleotides in length that negatively regulate coding gene [3] or long non-coding RNA (lncRNA) expression [4]. It is well documented that miRNAs are involved in diverse biological processes, including differentiation, proliferation, apoptosis, and tumorigenesis [5], [6]. Depending on their specific gene or lccRNA targets, miRNAs may function as oncogenes and/or tumor suppressors [7]. MiR-1 has been reported to function as a tumor suppressor in various cancers [8], [9], [10]. A previous report suggests that miR-1 may be a tumor suppressor in breast cancer [11]. However, the underlying mechanism of miR-1 in breast cancer development was still poorly explored.
In this study, K-RAS and lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were identified as targets of miR-1. The expression of miR-1 was negatively associated with K-RAS and MALAT1 in breast cancer tissues. MiR-1 inhibited breast cancer cell growth, induced apoptosis and decreased cell motility via regulating K-RAS and MALAT1.
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Cells culture and breast cancer patients tissues
MCF7 cells were purchased from the Cell Bank of the Shanghai Institutes for Biological Sciences (Chinese Academy of Sciences, Shanghai, China). SKBR3 and SKBR3-LR cells were kindly provided by Dr. Quanren Wang, as described previously [12].
A total of 139 female breast cancer patients who were diagnosed by histo-pathology in the Third Affiliated Hospital of Sun Yet-sen University from October 2006 to September 2011 were obtained. Specimens were formalin-fixed and embedded in paraffin by standard
MiR-1 and K-RAS/MALAT1 were inversely expressed in breast cancer tissues
The computational algorithms miRanda was used to search for potential miR-1 target genes. Among these candidate targets, we focused on K-RAS and MALAT1. First, we analyzed the relative expression levels of mature miR-1, K-RAS and MALAT1 by using real-time qPCR in 28 pairs of human breast cancer tissues and adjacent normal breast tissues. The results showed that miR-1 was down-regulated in breast cancer tissues compared with normal breast tissues (Fig. 1A). However, both K-RAS and MALAT1
Discussion
MiRNAs have been reported to regulate tumor migration, invasion and metastasis including breast cancer [19], [20]. miR-1 is consistently dysregulated across many cancers. We recently found that miR-1 exerted anti-angiogenic effect on nasopharyngeal carcinoma cells [16]. Additionally, recent studies have observed a functional contribution of miR-1 to cellular transformation, tumorigenesis, apoptosis, and drug sensitivity [21]. However, the role of miR-1 in breast cancer has not been fully
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