Background and aimSeveral dysregulated microRNAs (miRNAs) have been implicated in the pathogenesis of cholangiocarcinoma (CCA); however, small sample sizes and invariable research designs are limitations, hindering a thorough analysis of miRNAs as diagnostic and prognostic tools for CCA. This study aimed to systematically summarize the clinical value of miRNAs in human CCA both for all available miRNAs and single miRNA with multiple researches.MethodsPooled parameters included the area under the curve (AUC), sensitivity, specificity, and hazard ratios (HRs) to separately determine overall diagnostic and prognostic performance. Subgroup and sensitivity analyses were performed only in the event of heterogeneity. Thirty-four studies including 12 diagnostic studies and 22 prognostic studies were eligible for inclusion in this meta-analysis.ResultsWe observed that miR-21, miR-26, miR-483, miR-106a, miR-150, miR-192, and miR-194 were employed for distinguishing patients with CCA from healthy controls. Pooled sensitivity, specificity, and AUC were 0.82 (95% confidence interval [CI] 0.77–0.86), 0.83 (95% CI 0.75–0.89), and 0.88 (95% CI 0.85–0.91), respectively. Abnormal expression of miR-21, miR-26a, miR-192, miR-200c, miR-221, miR-29a, miR-191, miR-181c, miR-34a, miR-106a, miR-203, and miR-373 in patients was confirmed to associate with poor survival rate. Pooled HRs and 95% CIs were calculated using STATA, resulting in the pooled HR of 1.47 (95% CI 0.91–2.37) for overall survival (OS), 0.67 (95% CI 0.16–2.81) for disease-free survival (DFS), 2.31 (95% CI 1.59–3.36) for progression-free survival (PFS), and 2.68 (95% CI 0.88–8.15) for relapse-free survival (RFS). Thus, CCA patients with dysregulated miRNA expression were confirmed to have shorter OS, DFS, PFS, and RFS. Data regarding the diagnostic and prognostic roles of miR-21 suggested pooled diagnostic results of miR-21 for sensitivity, specificity, and AUC were 0.85 (95% CI 0.76–0.91), 0.92 (95% CI 0.81–0.97), and 0.93 (95% CI 0.91–0.95), respectively, suggesting better diagnostic performance of miR-21 compared with other miRNAs. Meanwhile, pooled prognostic result of miR-21 for HR was 1.88 (95% CI 1.41–2.51), indicating miR-21 could more appropriately predict shorter OS in patients with CCA.ConclusionmiRNAs may provide a new approach for clinical application, and miR-21 may be a promising biomarker for diagnosis and prognosis of CCA.
Prostate cancer (PCa) remains a leading cause of mortality among men in the United States and Western Europe. The molecular mechanism of PCa pathogenesis has not been fully elucidated. In the present study, the expression profile of E2F transcription factor 7 (E2F7) in PCa was examined using immunohistochemistry and reverse transcription-quantitative PCR, whilst cell cycle progression and apoptosis were determined using fluorescent cell activated sorting techniques. Cell viability was measured using Cell Counting Kit-8 in loss-and gain-of-function studies. Dual-luciferase reporter assay was used to verify if E2F7 was one of the potential targets of miR-30c. The staining score of E2F7 of PCa tissues was found to be notably higher compared with that of adjacent normal tissues. Suppression of E2F7 expression in PCa cell lines led to significantly reduced proliferation rates, increased proportion of cells in the G 1 phase of the cell cycle and higher apoptotic rates compared with those in negative control groups. Dual-luciferase reporter assay revealed E2F7 to be one of the binding targets of microRNA (miR)-30c. In addition, transfection of miR-30c mimics into PCa cells resulted in reduced cell viability, increased proportion of cells in the G 1 phase and higher apoptotic rates. By contrast, transfection with the miR-30c inhibitor led to lower apoptosis rates of PCa cells compared with negative control groups, whilst E2F7 siRNA co-transfection reversed stimulatory effects of miR-30c inhibitors on cell viability. In addition, the expression of cyclin-dependent kinase inhibitor p21 were found to be upregulated by transfection with either E2F7 siRNA or miR-30c mimics into PCa cells. In conclusion, the present study suggested that E2F7 may be positively associated with PCa cell proliferation by inhibiting p21, whereas E2F7 is in turn under regulation by miR-30c. These observations suggest the miR-30c/E2F7/p21 axis to be a viable therapeutic target for PCa.
Cancer stem cells (CSCs) are considered to serve a key role in tumor progression, recurrence and metastasis. Tumorsphere culture is the most important method for enriching CSCs and is widely used in basic research and drug screening. However, the traditional suspension cell culture system has several disadvantages, including low efficiency, high cost and difficult procedure, making it difficult to produce tumorspheres on a large scale. In the present study, two biomaterials, methylcellulose (MC) and gellan gum (GG), were used to construct a novel culture system based on the traditional system. Subsequently, the characteristics of the novel three-dimensional (3D) culture system were evaluated, the design scheme was optimized, and the morphological and biological features of the tumorspheres cultured in this 3D system were compared with the traditional system. The results revealed that the tumorspheres cultured in the novel 3D system presented a higher seeding density and improved morphology, while maintaining stem-like properties. This evidence suggests that a simple, efficient and low-cost culture system that produces tumorspheres on a large scale was successfully constructed, which can be widely used in various aspects of stem cell research.
BackgroundCasticin, an isoflavone compound extracted from the herb Fructus Viticis, has demonstrated anti-inflammatory and anticancer activities and properties. The aim of this study was to investigate the effects and mechanisms of casticin in nasopharyngeal carcinoma (NPC) cells and to determine its potential for targeted use as a medicine.MethodsNPC cells were used to perform the experiments. The CCK‑8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell cycle and apoptosis analysis (annexin V/PI assay). A three-dimensional (3D) tumour sphere culture system was used to characterize the effect of casticin on NPC stem cells. In silico molecular docking prediction and high-throughput KINOME scan assays were used to evaluate the binding of casticin to phosphoinositide 3-kinase (PI3K), including wild-type and most of mutants variants. We also used the SelectScreen assay to detect the IC50 of ATP activity in the active site of the target kinase. Western blotting was used to evaluate the changes in key proteins involved cell cycle, apoptosis, stemness, and PI3K/protein kinase B (AKT) signalling. The effect of casticin treatment in vivo was determined by using a xenograft mouse model.ResultsOur results indicate that casticin is a new and novel selective PI3K inhibitor that can significantly inhibit NPC proliferation and that it induces G2/GM arrest and apoptosis by upregulating Bax/BCL2 expression. Moreover, casticin was observed to affect the self-renewal ability of the nasopharyngeal carcinoma cell lines, and a combination of casticin with BYL719 was observed to induce a decrease in the level of the phosphorylation of mTORC1 downstream targets in BYL719-insensitive NPC cell lines.ConclusionCasticin is a newly emerging selective PI3K inhibitor with potential for use as a targeted therapeutic treatment for nasopharyngeal carcinoma. Accordingly, casticin might represent a novel and effective agent against NPC and likely has high potential for combined use with pharmacological agents targeting PI3K/AKT.
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