Guttilla We

Guttilla We.K., White. of SFRP1, up-regulation of Wnt, -catenin and GSK3, and promotion of cell proliferation, migration and invasion. The miR-27a inhibitor group showed up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the miR-27a mimic group. The si-SFRP1 + miR-27a Cesium chloride inhibitors group also exhibited up-regulation of SFRP1 and inhibition of cell proliferation, migration and invasion in comparison to the si-SFRP1 group. miR-27a may activate the Wnt/-catenin signaling pathway by negatively regulating SFRP1 to promote the proliferation, migration and invasion of BC cells. (DCIS) and invasive carcinoma [2]. Currently, for a vast majority of BC patients, mastectomy coupled with radiotherapy is usually widely put into practice for treatment with a relatively effective result [3]. However approximately10% of women diagnosed with BC exhibited a family history, so further studies concerning BC related genetic variants are necessary [4]. Wacholder et al. revealed that multiple genetic variants were associated with this type of cancer [5]. Although a large number of molecules have been reported as indicators in BC, their precise mechanisms remain to be brought to light. MicroRNAs (miRNAs), considered a novel class Cesium chloride of endogenous molecules, are non-protein coding small RNA molecules that can negatively regulate post-transcriptional gene expression by directly cleaving target mRNA or by inhibiting their translation [6]. A recent study has found that aberrant miRNAs expression is usually correlated to various human cancers such as colon tumors, breast malignancy and lung cancer [7]. MicroRNA-27a (miR-27a), located on chromosome 19, has been shown to have an oncogenic function Rabbit Polyclonal to RTCD1 in carcinomas by targeting prohibitin [8]. In addition, the Wnt/-catenin signaling pathway has also been found to exert an influence on a variety of cell biological processes, and its over-activation contributes to tumorigenesis, proliferation, and migration in several human cancers including breast malignancy [9]. Secreted frizzled-related proteins (SFRPs), serving as endogenous Wnt antagonists by binding directly to Wnts, have been demonstrated to either promote or suppress Wnt/-catenin signaling depending on the cellular context, concentration and the expression pattern of frizzled receptors. Interestingly, secreted frizzled-related proteins 1 (sFRP1) were reported as a novel target of miR-27a contributing to bone metabolism in hFOB cells [10]. Although several researches have been carried out in order to explore the effect of miR-27a or Wnt/-catenin signaling pathway on BC and the specific mechanisms [11, 12], it still remains unclear whether the role of miR-27 in proliferation and invasion of BC cells bears a relationship to the Wnt/-catenin signaling pathway via the regulation of SFRP1. Therefore, this study is intended to Cesium chloride shed light on the effects of miR-27a targeting SFRP1 on proliferation, migration and invasion of BC cells through regulating Wnt/-catenin signaling pathway. RESULTS The expression of miR-27a in BC tissues and its association to clinicopathological features of BC patients The levels of GAPDH mRNA in BC cancer and normal breast tissues were 16.2 0.31 and 15.83 0.29, respectively. The Ct values of RNU6 in BC cancer and normal breast tissues were 1.27 0.14 and 1.36 0.12, respectively. Results of RT-PCR revealed a remarkably higher expression of miR-27a in BC tissues than in normal breast tissues (= 0.023) (Physique ?(Figure1).1). No significant differences in the expression of miR-27a were found between patients older than 55-year-old and patients younger than 55-year-old, or between premenopausal patients and postmenopausal patients (both > 0.05). Expression of miR-27a was significantly higher in patients with distant metastasis than that in patients without distant metastasis (< 0.001). The relative expression of miR-27a n may be closely correlated to clinical stage and LNM as well as to tumor size (all < 0.001) (as shown in Table ?Table11). Open in a separate window Physique 1 The expression of miR-27a in normal breast and BC tissues as detected by qRT-PCRNote: normal breast tissues, n = 308; BC tissues, n = 396. miR-27a, microRNA-27a; BC, breast malignancy; qRT-PCR, quantitative real-time Cesium chloride polymerase chain reaction. Table 1 Association between miR-27a protein expression and clinicopathological features of patients with BC < 0.05). As a result T-47D cell line was selected for further experiment in this study (Physique ?(Figure22). Open in a separate window Physique 2.