BackgroundThe Hippo pathway is an essential signaling cascade that regulates cell and organ growth. However, there is no consensus about (i) the expression levels of the Hippo signaling core components yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in lung cancer, especially in small cell lung cancer (SCLC), or (ii) their association with the prognosis of patients with SCLC.MethodsWe screened relevant articles and identified eligible studies in the PubMed, EMBASE, COCHRANE, and WanFang databases. A combined analysis was performed to investigate (i) the expression levels of the major effectors, YAP and TAZ, in lung cancer and its subsets and (ii) their prognostic role in lung cancer, especially in SCLC.ResultsIn total, 6 studies related to TAZ and 13 studies concerning YAP were enrolled in this meta-analysis. We found that high TAZ expression was significantly associated with poor overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in the overall population [Ph < 0.001, crude hazard ratio (HR) = 1.629, 95% CI = 1.199–2.214 for TAZ expression; Ph = 0.029, adjusted HR = 2.127, 95% CI = 1.307–3.460 for TAZ], the Caucasian population (Ph = 0.043, crude HR = 1.233, 95% CI = 1.030–1.477 for TAZ expression), and the Asian population (Ph = 0.551, adjusted HR = 2.676, 95% CI = 1.798–3.982 for TAZ). Moreover, there was a significant negative association between YAP expression and an unsatisfactory survival of patients with lung cancer (Ph = 0.327, crude HR = 1.652, 95% CI = 1.211–2.253 for YAP expression) and patients with NSCLC [disease-free survival (DFS): Ph = 0.693, crude HR = 2.562, 95% CI = 1.876–3.499 for YAP expression; Ph = 0.920, crude HR = 2.617, 95% CI = 1.690–4.052 for YAP-mRNA; OS: Ph = 0.878, crude HR = 1.777, 95% CI = 1.233–2.562 for YAP expression], especially in the Asian population (DFS: Ph = 0.414, crude HR = 2.515, 95% CI = 1.755–3.063; OS: Ph = 0.712, crude HR = 1.772, 95% CI = 1.214–2.587). However, no association was observed in the multivariate combined analysis. High YAP expression was significantly associated with short OS of patients with SCLC in our combined multivariate analysis in the Asian population (Ph = 0.289, crude HR = 4.482, 95% CI = 2.182–9.209), but not with crude data (Ph = 0.033, crude HR = 1.654, 95% CI = 0.434–6.300).ConclusionThe Hippo pathway is involved in carcinogenesis and progression of NSCLC and SCLC, and high expression levels of YAP and TAZ are independent and novel prognostic factors for lung cancer.
Background Doxorubicin is a first‐line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance. Methods Quantitative reverse transcription‐PCR (qRT‐PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo. Results We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdown CrkL expression suppressed PI3K/Akt/MRP1 signaling, which indicated CrkL siRNA reversed doxorubicin effect through regulating PI3K/Akt/MRP1 pathway. In addition, overexpression of MRP1 could evidently reduce apoptosis rate and reversed the inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells. Finally, in vivo experiments revealed that CrkL silencing acted a tumor‐suppressing role in myelogenous leukemia via regulating PI3K/Akt/MRP1 signaling. Conclusion Together, we indicated that CrkL is up‐regulated in myelogenous leukemia cells and silencing of CrkL could reverse Doxorubicin resistance effectively. These results show a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.