To evaluate the impact of urothelial carcinoma with divergent differentiation (UCDD) on the prognosis of patients for primary upper urinary tract urothelial carcinoma (UTUC) with pN0/x status treated with radical nephroureterectomy (RNU) and to evaluate the prognostic value of UCDD in different tumor locations (renal pelvis and ureter).Data from a total of 346 patients with UTUC who received RNU between January 2012 and March 2016 in the institution were retrospectively analyzed. Clinicopathological features and prognostic factors age, sex, complaint, height, weight, blood pressure, tumor grade, stage, smoking status, history of adjuvant chemotherapy, tumor location, history of bladder cancer, tumor necrosis, degree of hydronephrosis, tumor size, tumor focality, and preoperative anemia were compared between patients with pure UTUC and patients with UCDD. The endpoints were cancer-specific survival (CSS), overall survival (OS), and intraluminal recurrence-free survival (IRFS).Overall, divergent differentiation was present in 50 patients (14.5%). UCDD was related to different tumor location (P = .01), smoking (P = .04), higher body mass index (P = .02), and advanced tumor grade (P = .01). By Kaplan–Meier analysis, UCDD was found to be significantly correlated with worse IRFS, CSS, and OS (all P < .01). Multivariate analysis demonstrated that UCDD was an independent predictor of IRFS (P < .01), CSS (P = .01), and OS (P = .01). However, 40 patients died for various reasons and the 5-year OS rates were 91.9% in UCDD− group and 68.0% in UCDD+ group, respectively. In patients with ureteral tumors, UCDD was the significant predictor for IRFS, CSS, and OS. However, the prognostic value of UCDD was not observed in pyelocaliceal tumors.The presence of divergent differentiation is associated with inferior survival. UCDD may identify patients at high risks for poor prognosis especially in patients with ureteral tumors. As a result, more attention and follow-up should be given to patients with ureteric urothelial carcinoma.

Purpose As the mechanism of interaction between circular RNAs (circRNAs) and microRNAs (miRNAs) in regulating the development of prostate cancer (PCa) is not clear, this study focuses on investigating these effects. Materials and Methods Sample tissues were collected from the PCa of patients, and microarray analysis of human circRNAs was conducted. The expression of circ_0001686, hsa_miR-411-5p (miR-411-5p) were also detected by qRT-PCR. Circ_0001686 and miR-411-5p mimics were transfected into the PCa cell lines (CWR22RV1and LNCaP) and MTT, colony formation, Transwell, and scratch wound assays were used to analyze the biological behaviors of PCa cells. Si-circ_0001686 and ASO-miR-411-5p were used as negative controls, and dual-luciferase reporter assays were performed to verify the interactions among circ_0001686, miR-411-5p, and SMAD3/TGFBR2. The levels of SMAD3 and TGFBR2 in different treated PCa cells were measured by western blot, and in vivo experiments in a nude mouse model were carried out to strengthen the in vitro findings of miR-411-5p. Results The expression of circ_0001686 was up-regulated, while the expression of miR-411-5p was down-regulated in PCa cells. Moreover, circ_0001686 promoted cell proliferation, migration, and invasion. Molecular mechanism exploration revealed that circ_0001686 could reduce miR-411-5p, affecting the downstream target genes of SMAD3 and TGFBR2. In vitro and in vivo studies verified that miR-411-5p inhibits PCa progression. Conclusions Circ_0001686 can reduce miR-411-5p to increase the expression of SMAD3/TGFBR2, which consequently promotes the proliferation, invasion, and migration of PCa cells.

Background: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo.Methods: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. Results: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014). Conclusions:We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145.The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.

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