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USP53 promotes apoptosis and inhibits glycolysis in lung adenocarcinoma through FKBP51-AKT1 signaling.

USP53 通过 FKBP51-AKT1 信号促进肺腺癌细胞凋亡并抑制糖酵解。

  • 影响因子:3.43
  • DOI:10.1002/mc.23230
  • 作者列表:"Zhao X","Wu X","Wang H","Yu H","Wang J
  • 发表时间:2020-06-08
Abstract

:Despite an overall decline in the incidence of new cases, lung adenocarcinoma continues to be a leading cause of cancer death worldwide. Due to lack of gene expression signatures for risk and prognosis stratification of lung adenocarcinoma, identifying novel molecular biomarkers and therapeutic targets may potentially improve lung adenocarcinoma prognosis and treatment. In the current study, we investigate the role of USP53 in lung adenocarcinoma. Bioinformatics analysis, quantitative reverse transcription polymerase chain reaction, and Western blot were employed to examine patterns of gene expression in human lung adenocarcinoma database, patient samples, and cancer cell lines. Stable cell lines were produced by transducing with USP53 overexpression vector or short hairpin RNA targeting USP53 in the presence and absence of AKT pathway inhibitor LY294002. Functional assays were carried out to examine the impact of USP53 and AKT pathway on lung adenocarcinoma cell viability, apoptosis, and glycolysis in vitro, as well as tumor growth in vivo. The correlation between USP53 and FKBP51 was measured by coimmunoprecipitation and ubiquitination assay. Decreased USP53 levels are a reliable marker of lung adenocarcinoma across published datasets, clinical samples, and cell culture lines. Low USP53 expression is linked to decreased apoptosis and increased metabolic activity, suggesting it acts as a tumor suppressor. USP53 regulates cell apoptosis and glycolysis through the AKT1 pathway. Mechanistically, USP53 deubiquitinates FKBP51, which in turn dephosphorylates AKT1, and ultimately inhibits tumor growth in lung adenocarcinoma. Taken together, our study establishes USP53 as a novel regulator of AKT1 pathway with an important role in tumorigenesis in lung adenocarcinoma.

摘要

: 尽管新病例的发生率总体下降,肺腺癌仍然是全球癌症死亡的主要原因。由于缺乏肺腺癌风险和预后分层的基因表达标签,确定新的分子生物标志物和治疗靶点可能潜在地改善肺腺癌预后和治疗。在目前的研究中,我们探讨 USP53 在肺腺癌中的作用。采用生物信息学分析、定量逆转录聚合酶链反应和 Western blot 检测人肺腺癌数据库、患者样本和癌细胞系的基因表达模式。在 AKT 通路抑制剂 ly294002 存在和不存在的情况下,用 USP53 过表达载体或靶向 USP53 的短发夹 RNA 转导产生稳定的细胞系。进行功能检测,以检测 USP53 和 AKT 通路对肺腺癌细胞体外活力、凋亡和糖酵解以及体内肿瘤生长的影响。采用免疫共沉淀和泛素化实验测定 USP53 与 FKBP51 的相关性。在已发表的数据集、临床样本和细胞培养株中,USP53 水平降低是肺腺癌的可靠标志物。低 USP53 表达与细胞凋亡减少和代谢活性增加有关,提示其作为肿瘤抑制因子。USP53 通过 AKT1 途径调节细胞凋亡和糖酵解。机制上,USP53 去泛素化 FKBP51,FKBP51 又去磷酸化 AKT1,最终抑制肺腺癌的肿瘤生长。总之,我们的研究建立了 USP53 作为 AKT1 通路的新调控因子,在肺腺癌的肿瘤发生中起重要作用。

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作者列表:["Esme H","Can A","Şehitogullari A"]

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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影响因子:8.44
发表时间:2020-02-01
DOI:10.1016/j.annonc.2019.10.022
作者列表:["Mazieres J","Cropet C","Montané L","Barlesi F","Souquet PJ","Quantin X","Dubos-Arvis C","Otto J","Favier L","Avrillon V","Cadranel J","Moro-Sibilot D","Monnet I","Westeel V","Le Treut J","Brain E","Trédaniel J","Jaffro M","Collot S","Ferretti GR","Tiffon C","Mahier-Ait Oukhatar C","Blay JY"]

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