MicroRNA-195-5p is a potential diagnostic and therapeutic target for breast cancer

Abstract

MicroRNAs (miRNAs) are a class of highly conserved, small endogenous single-strand non-coding RNAs. They are aberrantly expressed in the circulation and tissue of patients with cancer. Therefore, it has been suggested that they may act as key regulators of carcinogenesis. The aim of the present study was to examine the expression level of miR-195-5p in human breast cancer and its potential role in carcinogenesis. The expression level of miR-195-5p was measured in 40 breast cancer specimens and adjacent normal breast tissues by quantitative polymerase chain reaction (qPCR). Next, to explore the potential function of miR-195-5p, we used MDA-MB-231 human breast cancer cells and carried out MTT, colony formation, Transwell chamber migration and cell cycle assays. The dual-luciferase reporter assay was also performed to determine putative targets of miR-195-5p, which were validated using qPCR and western blot assays. We found that miR-195-5p expression was significantly decreased in the 40 breast cancer specimens when compared with that in the adjacent normal breast tissues (P<0.05). Overexpression of miR-195-5p inhibited cell proliferation, reduced cell colony formation, suppressed cell migration and caused an accumulation of cells in the G1 phase of the cell cycle. In the 3′-untranslated region (3′-UTR) of cyclin E1 (CCNE1), we found two putative target sites which may bind miR-195-5p, suggesting that CCNE1 is a direct target of miR-195-5p. Furthermore, through qPCR and western blot assays we showed that overexpression of miR-195-5p reduced CCNE1 mRNA and protein levels, respectively. Our study suggests that miR-195-5p may act as a tumor suppressor in breast cancer. Therefore, targeting of this miRNA may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease.

The NF-κB-modulated microRNAs miR-195 and miR-497 inhibit myoblast proliferation by targeting Igf1r, Insr and cyclin genes

“…Consistent with our results, recent studies have shown that miR-195 and miR-497 act as tumor suppressors by inhibiting multiple cell cycle regulators. miR-195 has been shown to directly target CCND1 and CCNE1 in human glioma and breast cancer (Hui et al, 2013;Luo et al, 2014), and both miR-195 and miR-497 have been shown to target CCND1, CCND3, CCNE1, CDC25A and CDK4 in human breast cancer and hepatocellular carcinoma (Furuta et al, 2013;Li et al, 2011). These results indicate that miR-195 and miR-497 can target many cell cycle genes and inhibit cell proliferation in both pathological and physiological conditions.…”

“…Consistent with this notion, miR-195 and miR-497 have been shown to be associated with various types of cancers. For example, miR-195 has been shown to act as a tumor suppressor in gastric cancer (Deng et al, 2013), hepatocellular carcinoma (Ding et al, 2013;Xu et al, 2009), bladder cancer (Lin et al, 2012), breast cancer (Luo et al, 2014;Singh and Saini, 2012), leukemia (Diaz-Beya et al, 2012) and other cancer types. miR-497 and miR-195 play similar roles in most physiological processes and miR-497 has also been found to be involved in tumorigenesis (Waters et al, 2012).…”

microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression

“…miR-195 has been reported to be downregulated in the tumor tissues and serum of cancer patients. miR-195 is involved in multiple processes during cancer development, including cell proliferation, migration, invasion and metastasis (7)(8)(9)(10)(11)(12). However, the function of miR-195 in cervical cancer development is unknown.…”

Identification of microRNA-regulated pathways using an integration of microRNA-mRNA microarray and bioinformatics analysis in CD34+ cells of myelodysplastic syndromes

“…Our in vitro experiments demonstrated that miR-195-5p overexpression promoted cell apoptosis and suppressed cell proliferation. Several previous studies revealed reduced miR-195-5p expression in many types of solid cancers, such as gastric, breast, and colon cancers202122. The overexpression of miR-195-5p in these cancers may inhibit cancer cell proliferation, migration and invasion.…”