Deubiquitinating enzymes (DUBs) serve to maintain cellular homeostasis via protein ubiquitination and exert diverse regulatory functions in cancers and other diseases. Much progress has been made in characterizing biological roles of DUBs over the decades, yet the specific functions of many subclass members remain largely unexplored. It was not until recent years that the role of ubiquitin-specific-processing protease 35 (USP35) in cancers began to be understood. Here, we focus on delineating the roles and underlying mechanisms of USP35 in non-small cell lung cancer (NSCLC). The isobaric tags for relative and absolute quantitation (iTRAQ) comparative proteomic approach were employed to identify differentially expressed proteins (DEPs) in H1299 cells induced by USP35 overexpression or silencing. Among the potential interactome of USP35, ribosome-binding protein 1 (RRBP1), a membrane-bound protein in endoplasmic reticulum (ER), captured our attentions. RRBP1 expression was found to positively correlate with USP35 levels in both genetically modified cells and human NSCLC tissues. Concordantly, both RRBP1 expression and USP35 expression were found to positively correlate with poor prognoses in lung adenocarcinoma patients. At the molecular level, USP35 was verified to directly interact with RRBP1 to prevent it from proteasomal-dependent degradation. Functionally, USP35 alleviated ER stress-induced cell apoptosis by stabilizing RRBP1 in NSCLC cells. Collectively, these findings indicate that USP35 plays a critical role in resisting ER stress-induced cell death through deubiquitinating RRBP1, hence providing a rationale to target the USP35-RRBP1 axis as an alternative therapeutic option for NSCLC.
Objective
Chronic kidney disease (CKD) is a major health‐care burden all over the world, and aging is an important risk factor for end‐stage renal disease (ESRD). Neutrophil gelatinase‐associated lipocalin (NGAL) has been confirmed as a novel marker for early diagnosis of acute kidney injury. Other studies have found that NGAL takes part in the mechanisms of CKD progression. The aim of this study was to evaluate the expression of serum NGAL in CKD, particularly in elderly patients who rapidly progressed to end‐stage renal failure.
Methods
Serum NGAL, cystatin C, creatinine, urea, and other factors were evaluated in a cohort of 160 CKD patients (mean age 75.29 ± 12.08 years) with various etiologies.
Results
Serum NGAL was closely related to cystatin C, creatinine, urea, and estimated glomerular filtration rate (eGFR). Special correlations between NGAL and, respectively, anemia and hypoalbuminemia were also found. The cutoff value of NGAL was calculated from Stage 2 to Stage 5. Receiver–operator curve analysis showed good area under the curve (>0.8) and high sensitivity (> 70%) on the cutoff value of NGAL. The NGAL levels increased progressively with the increasing of 2‐ and 5‐year risk of ESRD using the Kidney Failure Risk Equations (KFRE).
Conclusion
In elderly patients with CKD, serum NGAL reflects renal impairment and presents a strong and independent risk marker for progression of ESRD.
ObjectiveThe role of neutrophil gelatinase‐associated lipocalin (NGAL) for the evaluation of renal function in chronic kidney disease (CKD) has not yet to be determined. We aimed to perform a meta‐analysis exploring the correlation between NGAL and glomerular filtration rate (GFR) in CKD patients, and to further identify factors affecting NGAL's performance.MethodsStudies dated before November 2017 were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. A total of 28 relevant studies (involving 3082 patients from 17 countries) were included. The second version of the Quality Assessment for Studies of Diagnostic Accuracy demonstrated that no significant bias had influenced the methodological quality of the included studies.ResultsNeutrophil gelatinase‐associated lipocalin showed a strong negative correlation with measured glomerular filtration rate (mGFR). The pooled correlation coefficient (r) with corresponding 95% confidence intervals for the correlation between serum NGAL (sNGAL) and GFR was −0.48, meanwhile that for urine NGAL (uNGAL) and GFR was −0.34. However, NGAL's performance is different in subgroups restricted by clinical settings, race, sex, age, and staging of renal function.ConclusionNeutrophil gelatinase‐associated lipocalin could be a renal function evaluation marker for patients with renal dysfunction in CKD. Compared with uNGAL, there was a significant negative correlation between sNGAL and GFR. The performances of sNGAL and uNGAL were restricted by clinical factors that should be considered in regards to the sampling source selection.
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