BackgroundIn developed countries, prostate cancer (PCa) is a frequently diagnosed cancer with the second highest fatality rate. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) stably expressed in cells and involved in a series of carcinomas. However, few research studies have reported on the role of circRNAs in PCa.Material/MethodsWe used qRT-PCR to detect the expression of circMYLK (circRNA ID: hsa_circ_0141940) and miR-29a in PCa tissues and cell lines. MTT, colony formation, and TUNEL assays were performed to analysis the cell viability of PCa cells. Transwell and wound scratch assays were performed to investigate the cell invasion and migration of PCa cells.ResultsIn the present study, we confirmed that circMYLK expression level was significantly higher in PCa samples and PCa cells than in normal tissues and normal prostatic cells. The upregulated circRNA-MYLK promoted PCa cells proliferation, invasion, and migration; however, si-circRNA-MYLK significantly accelerated the PCa cell apoptosis. We also observed that the aforementioned function of circRNA-MYLK on PCa cells was affected through targeting miR-29a.ConclusionsWe confirmed circRNA-MYLK was an oncogene in PCa and revealed a novel mechanism underlying circRNA-MYLK in PC progression.

ObjectiveMicroRNA-100 (miR-100) has been demonstrated to be downregulated in bladder cancer tissues, and enforced expression of this miRNA may inhibit cell growth and colony formation of human bladder cancer 5637 cells in vitro. However, the clinical significance of miR-100 in human bladder cancer has not yet been elucidated. Thus, the aim of this study was to investigate the diagnostic and prognostic values of miR-100 in this disease.MethodsExpression levels of miR-100 in 126 pairs of bladder cancer and adjacent normal tissues were detected by TaqMan real-time quantitative RT-PCR assay. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis.ResultsExpression levels of miR-100 in bladder cancer tissues were significantly lower than those in adjacent normal tissues (mean expression level: 2.6 ± 1.2 vs. 3.9 ± 1.5, P < 0.001). When categorized into low vs. high expression, low miR-100 expression was negatively associated with the stage (P = 0.01), the recurrence (P = 0.008), the progression (P = 0.01), and the death (P < 0.001) of patients with bladder cancer. Moreover, low miR-100 expression clearly predicted poorer PFS (P = 0.001) and OS (P < 0.001). In the multivariate analysis, low miR-100 expression was an independent prognostic factor for both PFS (P = 0.01) and OS (P = 0.008).ConclusionOur data offer the convincing evidence that miR-100 may play an important role in the progression of bladder cancer and that the reduced expression of this miRNA may be independently associated with shorter PFS and OS of patients, suggesting that miR-100 might be a potential marker for further risk stratification in the treatment of this cancer.Virtual slidesThe virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1105483419841671

<b><i>Background:</i></b> Acute kidney injury (AKI) is a complex clinical disorder with sudden decay in renal function. Ischemia-reperfusion injury (IRI) has been regarded as the main etiology for the occurrence of AKI. MicroRNAs have been consistently shown to be involved AKI. <b><i>Objectives:</i></b> We aimed to investigate the role of miR-155 in AKI and its underlying mechanism. <b><i>Methods:</i></b> Ischemia-reperfusion (I/R)-induced AKI rat model and hypoxia-reoxygeneration (H/R)-induced NRK-52E cell model were established. The concentrations of serum creatinine and blood urea nitrogen were measured to evaluate renal function. Hematoxylin and eosin staining and TUNEL assay were performed to assess the severity of kidney injury. Additionally, quantitative real-time-PCR and western blot analysis were subjected to determine the expression of miR-155, TCF4, and apoptosis-related proteins, respectively. Moreover, cell proliferation and apoptosis were evaluated by Cell Counting Kit-8, bromodeoxyuridine, and flow cytometry analyses, respectively. Luciferase reporter assay was used to validate the direct targeting of TCF4 with miR-155. The protein levels of TCF4 and its downstream proteins in cells were measured by western blot. <b><i>Results:</i></b> The expression level of miR-155 was upregulated in both I/R-induced AKI rat model and H/R-treated NRK-52E cells. Moreover, overexpression of miR-155 promoted H/R-induced NRK-52E cells apoptosis and suppressed cell proliferation, while inhibition of miR-155 expression exerted opposite effects. Additionally, TCF4 was identified as a target of miR-155, of which expression was downregulated both in vivo and in vitro. Furthermore, the activity of Wnt/β-catenin signaling pathway was promoted following overexpression of TCF4 in NRK-52E cells, and this effect was attenuated by the increasing miR-155 expression. <b><i>Conclusion:</i></b> We demonstrated that miR-155 exacerbated AKI involving the targeting and regulation of TCF4/Wnt/β-catenin signaling pathway, indicating a novel regulatory network and elucidating a potential target for IRI-induced AKI treatment.

Prostate cancer metastasis is often associated with poor prognosis. The molecular coupling of the adaptor protein Crk to the docking protein p130Cas serves as a switch that regulates cell migration in several invasive cancer cells and Ack appears to act upstream of CrkII to modulate the cell motility. However, the precise role of Ack, Crk and p130Cas complex in prostate cancer migration remains unknown. In this study we examined the expression of Crk and p130Cas in prostate cancer cell lines, and found that CrkI and p130 Cas protein level was higher in highly invasive PC-3M and PC-3 cell lines than in moderately invasive DU-145 cells. Upon shRNA mediated knockdown of CrkI and p130Cas in PC-3M cells, cell migration and invasion were significantly inhibited as analyzed by wound healing assay and transwell invasion assay. Furthermore, co-immunoprecipitation assay showed that p130Cas interacted with CrkI in PC-3M cells and the stability of p130 Cas and CrkI depended on each other. AckI interacted with both CrkI and p130Cas and the interaction of AckI with CrkI seemed to be independent of p130 Cas . Taken together, our results demonstrate the high expression of CrkI and p130Cas in invasive prostate cancer cells and the important role of CrkI/p130Cas complex in the migration and invasion of prostate cancer cells. These data suggest that CrkI/p130 Cas could be exploited as potential molecular therapeutic target for prostate cancer metastasis.

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