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Although intravesical gemcitabine (GEM) chemotherapy (IGC) can effectively reduce the recurrence risk of non-muscle invasive bladder cancer (NMIBC), the development of GEM resistance may occur and result in cancer recurrence and disease progression. Herein, a label-free proteomics approach was used to characterize the proteomic profiles of primary/post-IGC recurrent NMIBC. A total of 218 proteins were found to be differentially expressed in paired primary and post-IGC recurrent NMIBC. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that multiple signaling pathways including \"focal adhesion\" were highly enriched in recurrent NMIBC. Niban apoptosis regulator 1 (NIBAN1) was identified as the top upregulated protein in recurrent NMIBC. Highly increased NIBAN1 expression was observed in a number of GEM-resistant cancer cell lines and in post-IGC recurrent NMIBC specimens. Manipulation of NIBAN1 expression affected the chemosensitivity to GEM in bladder cancer cell models. Moreover, NIBAN1 also regulated focal adhesion/focal adhesion kinase (FAK) signaling activation in bladder cancer cell lines. Highly elevated FAK (pY397) expression was observed in post-IGC recurrent NMIBC specimens, which was positively correlated with NIBAN1 expression. Knockdown of FAK markedly attenuated GEM resistance in GEM-resistant bladder cancer cells. studies demonstrated that knockdown of NIBAN1 disrupted FAK signaling and sensitized GEM-resistant bladder cancer cells to GEM treatment. Our findings suggest that NIBAN1 might regulate FAK signaling activation to promote GEM resistance in bladder cancer. Targeting NIBAN1/FAK signaling may help sensitize bladder cancer cells to GEM treatment.

Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by poor survival outcomes. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, monetary as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response. Here, we report the results of the first Exome-Wide Association Study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55,423 germline exonic SNPs to perform the analysis. We identified exome-wide significant ( p  < 9.02 × 10 − 7 ) associations for rs113985677 in CCIN with tamoxifen response, rs115400838 in TRMT5 with idelalisib response, rs11878277 in HDGFL2 with entinostat, and rs2229092 in LTA associated with vorinostat response. Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 in ATRAID , and rs11236938 in TSKU with the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level ( p  < 5 × 10 − 8 ). Additionally, a significant association of rs35704242 in NIBAN1 was associated with the combined response for nonchemotherapy medicines ( p  = 2.51 × 10 − 8 ), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the first EWAS to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.

Cell survival must quickly activate specific mechanisms that enable to detect changes in the cellular microenvironment. The impact of these cell alteration has direct consequences on cellular homeostasis. Cellular stress, as well as its regulation and implication, has been studied in different pathologies. In this sense, the alteration in NIBAN1 expression seems to act in response to different cellular disturbances. Over the years, the knowledge of NIBAN1 functions has improved, demonstrating its important cell roles, favoring the cell survival under stress context. In response to the disturbances, NIBAN1 seems to be involved in the decision-making process between cell survival and death. The increase in NIBAN1 expression has been related to cellular mechanisms that seek to minimize the damage caused to cellular homeostasis. In this review, the main biological insights attributed to the NIBAN1 gene in different cellular contexts and its role as a mediator of cellular stress are discussed.

Background: Nephronophthisis (NPH) is the most common genetic cause of end-stage renal disease (ESRD) in childhood, and NPHP1 is the major pathogenic gene. Cyst formation at the corticomedullary junction is a pathological feature of NPH, but the mechanism underlying cystogenesis is not well understood. The isolation and identification of cystic cell subpopulation could help to identify their origins and provide vital clues to the mechanisms underlying cystogenesis in NPH. Methods: Single-nucleus RNA sequencing (snRNA-seq) was performed to produce an atlas of NPHP1 renal cells. Kidney samples were collected from WT ( Nphp1 +/+ ) mice and NPHP1 ( Nphp1 del2-20/del2-20 ) model mice. Results: A comprehensive atlas of the renal cellular landscape in NPHP1 was generated, consisting of 14 basic renal cell types as well as a subpopulation of DCT cells that was overrepresented in NPHP1 kidneys compared to WT kidneys. GO analysis revealed significant downregulation of genes associated with tubular development and kidney morphogenesis in this subpopulation. Furthermore, the reconstruction of differentiation trajectories of individual cells within this subpopulation confirmed that a specific group of cells in NPHP1 mice become arrested at an early stage of differentiation and proliferate to form cysts. We demonstrate that Niban1 is a specific molecular marker of cystic cells in both mice and human NPHP1. Conclusion: In summary, we report a novel subpopulation of DCT cells, marked by Niban1, that are classified as cystic cells in the NPHP1 mice kidney. These results offer fresh insights into the cellular and molecular basis of cystogenesis in NPH.