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Background: Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments. Methods: Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies. Results: Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance. Conclusions: Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management. [ABSTRACT FROM AUTHOR]

Molecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node‐positive penile SCC. Patients with node‐positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer‐specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3‐CpG‐based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P <.001). The addition of the methylation score significantly improved the pN‐stage C‐index from 0.70 to 0.79 (incremental C = 0.09, P <.001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN‐stage C‐index from 0.69 to 0.78 (incremental C = 0.09, P <.001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node‐positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high‐risk group may benefit from more aggressive therapy or clinical trials. What's new? Patients with node‐positive penile cancer are not a homogeneous group, and new prognostic markers other than the pN stage are urgently needed. Here, the authors developed and validated a methylation score to predict survival outcome in node‐positive penile cancer. In pre‐inguinal lymphadenectomy patients, the risk score provides objective information supporting the decision‐making process for neoadjuvant therapy. In post‐inguinal lymphadenectomy patients, the risk score in conjunction with the pN stage can help tailor the multimodality treatment. The risk score can be easily measured from primary penis tumor samples and objectively evaluates the survival outcomes of patients, with an accuracy above 70%. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a primary malignant kidney cancer subtype. It has been suggested that long non-coding RNAs (lncRNAs) serve important roles in the progression of kidney cancer. In fact, the lncRNA small nucleolar RNA host gene 12 (SNHG12) was discovered to be overexpressed in various types of cancer. However, to the best of our knowledge, the role of SNHG12 in RCC remains unclear. The present study aimed to investigate the function of SNHG12 and its underlying molecular mechanism of action in RCC. In patient samples and datasets from The Cancer Genome Atlas. Reverse transcription-quantitative PCR, demonstrated that SNHG12 expression levels were upregulated in RCC tumor tissues, but not in normal kidney tissues. SNHG12 upregulation was also observed in RCC cell lines. Kaplan-Meier survival analysis indicated a poor prognosis for those patients with RCC who had upregulated SNHG12 expression levels. Following lentivirus transduction, SNHG12 was successfully knocked down (validated by western blot analysis) and cell migration and invasion assays were performed. SNHG12 knockdown markedly inhibited cell viability and invasion, while increasing apoptosis in both A498 and 786O cell lines. The results of the luciferase reporter assay suggested that SNHG12 exerted its role by sponging microRNA (miR)-200c-5p, which led to the upregulation of its target gene, collagen type XI α1 chain (COL11A1). This was further validated, as miR-200c-5p inhibition reduced the effects of SNHG12 downregulation on cell viability and apoptosis, without affecting SNHG12 expression levels. Furthermore, the findings indicated that SNHG12 may partially exert its role through COL11A1, which was also upregulated in RCC. In conclusion, the results of the present study suggested that the SNHG12/miR-200c-5p/COL11A1 axis may be crucial for RCC progression, which provided an insight into potential therapeutic strategies for RCC treatment. [ABSTRACT FROM AUTHOR]

Experimental investigation of the elastic behaviours of lacustrine shales remains sparse, although they play an essential role in source rock evaluation, unconventional reservoir exploration and development, and the seal integrity evaluation for geological storage of CO2 and nuclear waste disposal. We make the ultrasonic velocity measurement of 63 organic‐rich shale samples (Chang 7, Qingshankou and Lucaogou formation) from three typical lacustrine basins in China. It is found that the P‐ and S‐wave velocity of Chang 7 and Qingshankou shale corresponding to the fresh‐brackish lacustrine depositional environment is mainly impacted by the clay and organic matter content, whereas their elastic anisotropic magnitude is mostly influenced by clay content. The P‐ and S‐wave velocities of Lucaogou shale corresponding to the saline lacustrine depositional environment are mainly affected by the total organic carbon and porosity and exhibit weak anisotropy linked to organic matter enrichment. Exponential law well captures the relationship between anisotropic magnitude and velocity perpendicular to bedding for both saline and fresh‐brackish water lacustrine shales, although there exists notable discrepancy, particularly at low velocities. The disparity in elasticity between laminations has a profound impact on the magnitude of elastic anisotropy and shapes the trend of velocity variations. [ABSTRACT FROM AUTHOR]