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Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in cancer development and progression. However, the mechanism by which they enhance the chemoresistance of ovarian cancer is unknown. Methods: Conditioned media of BM-MSCs (BM-MSC-CM) were analyzed using a technique based on microRNA arrays. The most highly expressed microRNAs were selected for testing their effects on glycolysis and chemoresistance in SKOV3 and COC1 ovarian cancer cells. The targeted gene and related signaling pathway were investigated using in silico analysis and in vitro cancer cell models. Kaplan-Merier survival analysis was performed on a population of 59 patients enrolled to analyze the clinical significance of microRNA findings in the prognosis of ovarian cancer. Results: MiR-1180 was the most abundant microRNA detected in BM-MSC-CM, which simultaneously induces glycolysis and chemoresistance (against cisplatin) in ovarian cancer cells. The secreted frizzled-related protein 1 (SFRP1) gene was identified as a major target of miR-1180. The overexpression of miR-1180 led to the activation of Wnt signaling and its downstream components, namely Wnt5a, β-catenin, c-Myc, and CyclinD1, which are responsible for glycolysis-induced chemoresistance. The miR-1180 level was inversely correlated with SFRP1 mRNA expression in ovarian cancer tissue. The overexpressed miR-1180 was associated with a poor prognosis for the long-term (96-month) survival of ovarian cancer patients. Conclusions: BM-MSCs enhance the chemoresistance of ovarian cancer by releasing miR-1180. The released miR-1180 activates the Wnt signaling pathway in cancer cells by targeting SFRP1. The enhanced Wnt signaling upregulates the glycolytic level (i.e. Warburg effect), which reinforces the chemoresistance property of ovarian cancer cells.
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<p><b>OBJECTIVE</b>This study aimed to investigate the expression and correlation of secreted frizzled-related protein 1 (SFRP1) and β-catenin in gingival tissues of patients with chronic periodontitis (CP). The role of the classical Wnt/β-catenin signaling pathway in the development of periodontitis was also explored.</p><p><b>METHODS</b>Twenty-eight patients with CP (CP group) were enrolled in this study. Among them, 16 cases were moderate CP, and 12 demonstrated severe CP. Twelve healthy cases comprised the controls (normal group). Gingival tissue was collected, and the probing depth, bleeding index, and clinical attachment loss were recorded. The expression levels of SFRP1 and β-catenin were detected by immunohistochemistry, and staining intensity was evaluated by double scoring method. SPSS 19.0 was used for statistical analysis.</p><p><b>RESULTS</b>The staining strength scores of SFRP1 and β-catenin were 2.16±0.65 and 1.12±0.51 in the normal group, 3.57±0.45 and 2.36±0.49 in the CP group, 3.61±0.40 and 2.30±0.44 in the moderate CP group, and 3.52±0.52 and 2.45±0.55 in the severe CP group, respectively. The expression of SFRP1 and β-catenin in the CP group was higher than that in the normal group (P<0.01). A significant difference was noted between the normal group and the moderate and severe CP groups (P<0.01) but none between the moderate and severe CP groups (P>0.05). A positive correlation was found between the expression of SFRP1 and β-catenin (r=0.657, P<0.01). The expression levels of β-catenin and SFRP1 were related to periodontal indexes. The correlation between the expression of SFRP1 and probing depth was most significant (r=0.723, P<0.01), as well as that between β-catenin and bleeding index (r=0.697, P<0.01).</p><p><b>CONCLUSIONS</b>Patients with CP exhibit elevated expression of SFRP1 and β-catenin in gingival tissues, and this event is related to the degree of periodontal destruction. Abnormal expression of SFRP1 and β-catenin may promote the development of periodontitis.</p>
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Objective To measure the expression of SFRP1 in bladder cancer and explore the corresponding mechanism,in order to study the roles of SFRP1 in the pathogenesis of bladder cancer.Methods SFRP1 mRNA was detected by RT-PCR.Methylation status of SFRP1 was detected by methylation specific PCR.SFRP1 protein was determined by Western blotting.Results SFRP1 was methylated in bladder cancer cell lines T24 and 5637,not in SCaBER.SFRP1 mRNA and protein were detected in SCaBER,but not in T24 and 5637.Six hours after treating T24 and 5637 with 5'-aza-deoxycytidine,both T24 and 5637 expressed SFRP1 mRNA and protein.In 45 bladder cancers,methylation of SFRP1 was detected in 28 (62.2％).In matched cancer adjacent tissues,6 (13.3％) were found with SFRP1 methylation.The methylation rate in bladder cancers was significant higher than that in matched cancer adjacent tissues (P ＜ 0.01).Conclusions SFRP1 is downregulated in some bladder cancers due to methylation.SFRP1 methylation and aberrant expression may be involved in the pathogenesis of bladder cancers.