BackgroundSurvivin (encoded by the gene BIRC5) plays an important role in the carcinogenesis of bladder cancer. Identifying miRNAs that target Survivin in the setting of bladder cancer will help to develop Survivin-based therapies for bladder cancer.MethodsThe expression levels of miR-138-5p and Survivin protein were measured in 12 resected bladder cancer specimens. The correlation between miR-138-5p and Survivin was further examined by evaluating Survivin expression in human bladder cancer cell lines that either overexpressed or knocked down miR-138-5p. A luciferase reporter assay was performed to test the direct binding of miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder cancer cell lines both in vivo and in vitro.ResultsIn this study, we found that the Survivin protein was either absent or weakly expressed in normal adjacent tissues and consistently up-regulated in bladder cancer tissues; however, the mRNA levels did not vary as much, suggesting that a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that could potentially target BIRC5 in the setting of bladder cancer. We identified 2 specific targeting sites for miR-138-5p in the 3′ untranslated region (3′-UTR) of BIRC5. We further identified an inverse correlation between miR-138-5p and Survivin protein levels in bladder cancer tissue samples. By overexpressing or knocking down miR-138-5p in bladder cancer cells, we experimentally confirmed that miR-138-5p directly recognizes the 3′-UTR of the BIRC5 transcript and regulates Survivin expression. Furthermore, the biological consequences of the targeting of BIRC5 by miR-138-5p were examined in vitro via cell proliferation and invasion assays and in vivo using a mouse xenograft tumor model. We demonstrated that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder cancer cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model.ConclusionsTaken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder cancer by inhibiting BIRC5 translation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0569-4) contains supplementary material, which is available to authorized users.

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Different from conventional vaccines, in situ vaccination could conveniently convert established tumors into a "vaccine factory" to release various tumor antigens for stimulating and diversifying antitumor T-cell response. [3] Radiation therapy (RT) is a widely used local therapy of malignancies and exhibits great potential in inducing in situ tumor vaccine effect. [4] However, even potentiated by CBI, RT could only lead to mild to moderate immune response within nonirradiated tumors, which is far less than medical needs. [5] Therefore, it is quite meaningful to boost RT-mediated in situ vaccination to extend its therapeutic effect to the whole body.To achieve this goal, a possible way could be potentiating RT-induced immunogenic cell death (ICD). ICD is a death modality accompanied by releasing tumor antigens and damage-associated molecular patterns, including calreticulin (CRT), high mobility group protein B1 (HMGB1), etc., which could provide antigens and adjuvants for tumor vaccination. [6] Currently, some studies have indicated that oxidative stress and DNA damage within tumor cells could potentially result in ICD. [7] However, due to the insufficient deposition of X-ray within tumor tissues, only low level of reactive oxygen species (ROS) could be produced to induce oxidative stress upon the recommended radiation doses. To address this problem, radiosensitizers based on high-Z elements are being developed widely to deposit X-ray for amplifying RT-induced oxidative stress. Of note, HfO 2 nanoparticles (Hensify) have been approved in Europe for locally advanced soft tissue sarcoma treatment [8] and are confirmed to augment RT-mediated antitumor immunity effect in many clinical trials. However, their slight improvements suggest the room for optimization. [9] The pentose phosphate pathway (PPP) is a branch of glycolysis and hyperactive in most tumors, [10] which could provide abundant NADPH and ribose 5-phosphate to maintain redox and nucleotides homeostasis, respectively. [11] NADPH is a central player in cellular antioxidant system, which not only mediates GSH synthesis, [12] but also acts as an electron donor to reduce oxidized GSH and thioredoxin (Trx, an important In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic tumor cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity for establishing efficient in situ vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor of the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) nanosheets to boost radiation-therapy (RT)-induced immunogenic cell death (ICD) for potent in situ tumor vaccination. It is first observed that sheet-like PLGdH can present superior X-ray deposition and tumor penetrability, exhibiting improved radiosensitization in vitro and in vivo. Moreover, the destruction of cellular nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotide...

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ObjectivesThis study was intended to analyze effects of miR-199a-3p and Smad1 on proliferation, migration and invasion of prostate cancer (PCa) cells.ResultsMiR-199a-3p was significantly decreased in PCa tissues in comparison to that in adjacent normal tissues (P < 0.05). Over-expressed miR-199a-3p markedly suppressed proliferation and invasion of PCa cells (P < 0.05). MiR-199a-3p was negatively correlated with Smad1 expression, and overexpression of Smad1 could antagonize the effects of miR-199a-3p on PCa cells.Materials and methodsThe PCa tissues and their adjacent normal tissues were collected from 54 PCa patients. Expressions of miR-199a-3p and Smad1 mRNA in tissues and cells were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry assay was used to detect Smad1 protein expressions. The target relationship between miR-199a-3p and Smad1 was assessed by luciferase reporter assay. The PCa cell lines (i.e. PC-3 cells) were transfected with miR-199a-3p mimics and Smad1-cDNA. MTT and Transwell assays were applied to detect proliferative, migratory and invasive abilities of PCa cells.ConclusionsMiR-199a-3p suppressed proliferation and invasion of PCa cells by targeting Smad1.

BackgroundTo compare the complications of traditional transrectal (TR) prostate biopsy and image fusion guided transperineal (TP) prostate biopsy in our center.MethodsTwo hundred and fourty-two patients who underwent prostate biopsy from August 2014 to January 2015were reviewed. Among them, 144 patients underwent systematic 12-core transrectal ultrasonography (TRUS) guided prostate biopsy (TR approach) while 98 patients underwent free-hand transperineal targeted biopsy with TRUS and multi-parameter magnetic resonance imaging (mpMRI) fusion images (TP approach). The complications of the two groups were presented and a simple statistical analysis was performed to compare the two groups.ResultsThe cohort of our study include242 patients, including 144 patients underwent TR biopsies while 98 patients underwentTP biopsies. There was no significant difference of major complications, including sepsis, bleeding and other complication requiring admissionbetween the two groups (P > 0.05). The incidence rate of infection and rectal bleeding in TR was much higher than TP (p < 0.05), but the incidence rate of perineal swelling in TP was much higher than TR (p < 0.05). There were no significant differences of minor complications including hematuria, lower urinary tract symptoms (LUTS), dysuria, and acuteurinary retention between the two groups (p > 0.05).ConclusionThe present study supports the safety of both techniques. Free-handTP targeted prostate biopsy with real-time fusion imaging of mpMRI and TR ultrasound is a good approach for prostate biopsy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12894-016-0185-z) contains supplementary material, which is available to authorized users.