Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies in the world, and tumor metastasis is still the main reason for disease progression. Accumulating evidence shows that SH3BGRL2 may play a key role in tumor progression and metastasis. However, the role of SH3BGRL2 in ccRCC has not been systematically investigated and remains elusive. The clinical significance of SH3BGRL2 was evaluated by bioinformatic analysis and tissue microarray (TMA) samples. SH3BGRL2 expression was determined by RT-PCR, western blot and immunohistochemistry staining. Tumor suppressive effect of SH3BGRL2 was determined by both in vitro and in vivo studies. Western blot, chromatin immunoprecipitation assay and luciferase report assay were applied for mechanism dissection. SH3BGRL2 was crucial for epithelial-mesenchymal transition (EMT) progression and metastasis in ccRCC. Clinically, SH3BGRL2 was identified as an independent prognostic factor for ccRCC patients. Gain- and loss-of-function results suggested that SH3BGRL2 played a critical role in cell proliferation, migration and invasion. Mechanistically, we found that SH3BGRL2 acted as a tumor suppressor through Hippo/TEAD1 signaling, then TEAD1 altered Twist1 expression at the transcriptional level via directly binding to its promoter region. Our findings established that SH3BGRL2 performed as a tumor suppressor and modulator via Hippo/TEAD1-Twist1 signaling in ccRCC, and the alteration of SH3BGRL2 could serve as a functional response biomarker of tumor progression and metastasis in ccRCC.

Lymphatic metastasis is recognized as the leading manner of metastasis in bladder cancer (BLCa), but hematogenous metastasis accounts for a majority of cancer-associated deaths. The past two decades have witnessed tremendous attention in long non-coding RNAs (lncRNAs), which are a new hope for the development of targeted drug therapy for metastatic cancers; however, the underlying mechanism of lncRNAs involved in BLCa hematogenous metastasis remains to be elucidated. Here, we identified BLCa-associated transcript 3 (BLACAT3), a lncRNA, which was aberrantly upregulated in BLCa and corelated with poor prognosis of patients with muscle-invasive bladder cancer. Methodologically, m6A epitranscriptomic microarray, RNA sequencing and mass spectrometry (MS) were used to screen the key molecules of the regulatory axis. Functional assays, animal models and clinical samples were used to explore the roles of BLACAT3 in BLCa in vitro and in vivo. Mechanistically, m6A modification contributes to BLACAT3 upregulation by stabilizing RNA structure. BLACAT3 recruits YBX3 to shuttle into the nucleus, synergistically enhances NCF2 transcription, and promotes BLCa angiogenesis and hematogenous metastasis by activating downstream NF-κB signaling. Our findings will develop prognosis prediction tools for BLCa patients and discover novel therapeutic biological targets for metastatic BLCa.

Background: Kidney Renal Clear Cell Carcinoma (KIRC) accounts for 75% of all renal cancers. Previous study had conflict evidences regarding NR1B2 role in cancer, and its expression and biological role in KIRC remained unclear. Our aims were to characterize the role of NR1B2 in KIRC. Methods: NR1B2 expression in TCGA database were analyzed. Clinical KIRC samples were examined by RT-PCR, western blot and tissue microarray (TMA). The relationship between NR1B2 expression and the clinical characteristics were evaluated. KIRC cell line were stably overexpressed NR1B2 or with an NR1B2 knocked down using lentivirus system. The cells were analyzed by migration and invasion assay, then injected into nude mice to assess tumor growth and metastasis. EMT marker expression and LATS 1/2-YAP pathway demonstration were detected by the TCGA database and western blot. Results: The expression of NR1B2 in KIRC was significantly down-regulated in the TCGA database and our clinical samples. Moreover, NR1B2 expression negatively correlated with tumor stage and positively correlated with overall and disease-free survival rate. Univariate and multivariate analyses indicated the expression level of NR1B2 could be used as an independent factor for predicting the prognosis of KIRC. Overexpression NR1B2 significantly inhibited and knockdown NR1B2 markedly promoted KIRC cell invasion and metastasis both in vitro and in vivo. Mechanistic investigations revealed that NR1B2 might be a tumor suppressor to inhibit EMT through the LATS1/2-YAP pathway. Conclusions: our results defined NR1B2 as a tumor suppressor in KIRC that restricted EMT by the LATS1/2-YAP pathway.

Purpose To investigate the association between sarcopenia and overactive bladder (OAB) in a United States adult population from 2011 to 2018, and whether sarcopenia can predict the risk of OAB. Materials and Methods We analyzed data from the 2011–2018 National Health and Nutrition Examination Survey in a crosssectional study(NHANES) of 8746 participants, of whom 1213 were diagnosed with OAB, we analyzed correlations by sex, age, race, education level, marital status, household income-to-poverty ratio, hypertension, diabetes, strenuous work activity, moderate work activity, strenuous recreational activity, moderate recreational activity, blood urea nitrogen, creatinine, and uric acid levels using restricted cubic spline plots of dose-response curves, univariate and multivariate Logistic regression. Models based on sex, age, education, household income to poverty ratio, hypertension, diabetes, sarcopenia index, and cotinine were developed and evaluated using Nomogram, calibration curves, receiver operating characteristic curves, and clinical decision curves. Results Of the 1213 OAB patients, 388 (32.0%) were male and 825 (68.0%) were female. Univariate and multivariate Logistic regression analysis showed that sarcopenia index was negatively correlated with the prevalence of OAB (OR=0.084, 95% CI, 0.056–0.130, P <0.001;OR=0.456, 95%CI, 0.215–0.968, P= 0.0041). Dose curve analysis of the sarcopenia index and prevalence of OAB showed that the prevalence of OAB decreased significantly with increasing sarcopenia index. Sarcopenia was positively correlated with OAB (OR=2.400, 95%CI, 2.000–2.800, P <0.001;OR=1.46, 95%CI, 1.096 −1.953, P = 0.010). In addition, our model shows that sarcopenia can predict the prevalence of OAB (AUC = 0.750) and has some clinical decision-making implications. Conclusion Sarcopenia is positively associated with the risk of OAB in United States adults and can be used as a predictor of OAB prevalence.

Reactive oxygen, nitrogen, sulfur, carbonyl, chlorine, bromine, and iodine species (RXS, X = O, N, S, C, Cl, Br, and I) play important roles in normal physiological processes through governing cell signaling, immune balance, and tissue homeostasis.