Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods: The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results: SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion: This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.

The gold standard for prostate cancer (PCa) diagnosis is prostate biopsy. However, it remines controversial as an invasive mean for patients with PSA levels in the gray zone (4–10 ng/mL). This study aimed to develop strategy to reduce the unnecessary prostate biopsy. We retrospectively identified 235 patients with serum total PSA testing in the gray zone before prostate biopsy between 2014 and 2018. Age, PSA derivates, prostate volume and multiparametric magnetic imaging (mpMRI) examination were assessed as predictors for PCa and clinically significant PCa with Gleason score ≥ 7 (CSPCa). Univariate analysis showed that prostate volume, PSAD, and mpMRI examination were significant predictors of PCa and CSPCa (P < 0.05). The differences of diagnostic accuracy between mpMRI examination (AUC = 0.69) and other clinical parameters in diagnostic accuracy for PCa were not statistically significant. However, mpMRI examination (AUC = 0.79) outperformed prostate volume and PSAD in diagnosis of CSPCa. The multivariate models (AUC = 0.79 and 0.84 for PCa and CSPCa) performed significantly better than mpMRI examination for detection of PCa (P = 0.003) and CSPCa (P = 0.036) among patients with PSA level in the gray zone. At the same level of sensitivity as the mpMRI examination to diagnose PCa, applying the multivariate models could reduce the number of biopsies by 5% compared with mpMRI examination. Overall, our results supported the view that the multivariate model could reduce unnecessary biopsies without compromising the ability to diagnose PCa and CSPCa. Further prospective validation is required.

The antiproliferation effect of deuterium depleted water (DDW) is well documented, but the mechanism remained elusive. Here three complementary proteomics approaches applied to A549 cells revealed a disbalance brought about by DDW in mitochondria between ROS production and neutralization, thus leading to oxidative stress in the cells. Subsequent validation by orthogonal approaches supported this scenario. Therefore, DDW has potential as an adjuvant in antitumor therapy, especially in the modalities inducing oxidative stress in cancer cells.

Responses of transpiration (Ec) to rain pulses are presented for two semiarid tree species in a stand of Pinus tabulaeformis and Robinia pseudoacacia. Our objectives are to investigate (1) the environmental control over the stand transpiration after rainfall by analyzing the effect of vapor pressure deficit (VPD), soil water condition, and rainfall on the post-rainfall Ec development and recovery rate, and (2) the species responses to rain pulses and implications on vegetation coverage under a changing rainfall regime. Results showed that the sensitivity of canopy conductance (Gc) to VPD varied under different incident radiation and soil water conditions, and the two species exhibited the same hydraulic control (-dG c/dlnVPD to Gcref ratio) over transpiration. Strengthened physiological control and low sapwood area of the stand contributed to low Ec. VPD after rainfall significantly influenced the magnitude and time series of post-rainfall stand Ec. The fluctuation of post-rainfall VPD in comparison with the pre-rainfall influenced the Ec recovery. Further, the stand Ec was significantly related to monthly rainfall, but the recovery was independent of the rainfall event size. Ec enhanced with cumulative soil moisture change (ΔVWC) within each dry-wet cycle, yet still was limited in large rainfall months. The two species had different response patterns of post-rainfall Ec recovery. Ec recovery of P. tabulaeformis was influenced by the pre- and post-rainfall VPD differences and the duration of rainless interval. R. pseudoacacia showed a larger immediate post-rainfall Ec increase than P. tabulaeformis did. We, therefore, concluded that concentrated rainfall events do not trigger significant increase of transpiration unless large events penetrate the deep soil and the species differences of Ec in response to pulses of rain may shape the composition of semiarid woodlands under future rainfall regimes.

Background: Accumulating evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. Cancer susceptibility candidate 9 (CASC9) is a novel long noncoding RNA and plays important regulatory role in diverse biological processes of cancers. However, the clinical significance and molecular mechanism of CASC9 in bladder cancer is still unknown. Methods: Comprehensive lncRNAs profiling analysis were conducted to identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer. The expression level of CASC9 was determined in a total of 106 patients with bladder cancer. Loss-of-function experiments were performed to identify the functions of CASC9 in tumor growth and metastasis of bladder cancer in vitro and in vivo. Bioinformatics analysis and further experiments were performed to explore the molecular mechanisms underlying the functions of CASC9. Results: This study found that CASC9 expression was markedly upregulated in bladder cancer and related to histological grade, TNM stage and prognosis. Knockdown of CASC9 inhibited tumor growth and metastasis of bladder cancer in vitro and in vivo. Mechanistically, we found that CASC9 functions as a miRNA sponge to positively regulate FZD6 expression and subsequently activates Wnt/β-catenin signaling pathway, thus playing an oncogenic role in bladder cancer pathogenesis. Conclusion: In summary, lncRNA CASC9 plays a critical regulatory role in bladder cancer. The CASC9/miR-497-5p/ FZD6 axis provides insights for regulatory mechanism of bladder cancer, and new strategies for clinical practice.