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WTAP/CCND1 axis accelerates esophageal squamous cell carcinoma progression by MAPK signaling pathway. WTAP/CCND1轴通过MAPK信号通路加速食管鳞状细胞癌的进展。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-08-01 DOI: 10.4149/neo_2024_231219N653
Hong Zhang, Xiaojing Zhang, Yan Zhang, Jianhua Wu, Jiali Li, Baoen Shan

N6-methyladenosine (m6A) methylation, as a new regulatory mechanism, has been reported to be involved in diverse biological processes in recent years. Wilms tumor 1-associated protein (WTAP), as the key member of m6A methylation, has been proven to participate in tumorigenesis. Here, we studied the expression of WTAP and its potential mechanism involved in the development of esophageal squamous cell carcinoma (ESCC). We detected the expression of WTAP and its correlation with clinicopathological features, and we determined the function of WTAP on ESCC cells by MTS assay, colony formation, scratch wound healing assay, Transwell assay, and subcutaneous xenograft assay. We used mRNA sequencing technology to screen candidate downstream targets for WTAP and investigated the underlying mechanism of CCND1 in ESCC promotion through a series of rescue assays. An elevated expression of WTAP in ESCC malignancy indicated a worse prognosis. WTAP promoted the proliferation and metastasis of ESCC cells, and CCND1 was identified as the potential downstream effecter of WTAP. Moreover, WTAP modulated ESCC progression through a MAPK pathway-dependent pattern. Our research suggested that WTAP promoted both proliferation and metastasis of ESCC by accelerating the expression of CCND1 via the MAPK signaling pathway, indicating that WTAP may be a candidate prognostic biomarker for ESCC and also will be a promising strategy for ESCC cancer therapy.

近年来,N6-甲基腺苷(m6A)甲基化作为一种新的调控机制,被报道参与了多种生物过程。Wilms tumor 1-associated protein(WTAP)作为 m6A 甲基化的关键成员,已被证实参与了肿瘤的发生。在此,我们研究了 WTAP 的表达及其参与食管鳞状细胞癌(ESCC)发生的潜在机制。我们检测了 WTAP 的表达及其与临床病理特征的相关性,并通过 MTS 试验、集落形成试验、划痕伤口愈合试验、Transwell 试验和皮下异种移植试验确定了 WTAP 对 ESCC 细胞的作用。我们利用 mRNA 测序技术筛选了 WTAP 的候选下游靶点,并通过一系列挽救实验研究了 CCND1 促进 ESCC 的内在机制。WTAP在ESCC恶性肿瘤中的表达升高表明预后较差。WTAP促进了ESCC细胞的增殖和转移,而CCND1被确定为WTAP的潜在下游效应器。此外,WTAP通过MAPK通路依赖模式调节ESCC的进展。我们的研究表明,WTAP通过MAPK信号通路加速CCND1的表达,从而促进了ESCC的增殖和转移,这表明WTAP可能是ESCC的一种候选预后生物标志物,也将是ESCC癌症治疗的一种有前途的策略。
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引用次数: 0
Downregulation of WNK4 expression facilitates the proliferation of gastric cancer cells via activation of the STAT3 signaling pathway. 下调 WNK4 的表达可通过激活 STAT3 信号通路促进胃癌细胞的增殖。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.4149/neo_2024_240220N67
Miao Li, Xiaoyan Shao, Qiqi Ning, Rongrong Sun, Rantian Li, Yanhua Liu, Yuan Yuan, Youwei Zhang

WNK lysine deficient protein kinase 4 (WNK4) has been shown to be significantly associated with cancer progression. Nevertheless, its involvement in gastric cancer (GC) is unclear. The objective of this work was to investigate the WNK4's regulatory mechanism in GC. Quantitative RT-PCR and immunoblots revealed that WNK4 expression was downregulated in GC and that low expression of WNK4 was strongly linked to poor prognosis. Functional assays including cell counting kit-8 assay and colony formation assay demonstrated that overexpression of WNK4 led to limited tumor proliferation both in vitro and in vivo, while the WNK4 reduction yielded to the opposite results. Gene Set Enrichment Analysis (GSEA) indicated a potential association between WNK4 and the signal transducer and activator of transcription (STAT3). WNK4 suppressed the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in GC cells. The inhibition of the STAT3 pathway with Stattic reversed growth and proliferation induced by WNK4 knockdown in GC cells. These findings provide new insights for identifying key therapeutic targets for GC in the future.

WNK 赖氨酸缺陷蛋白激酶 4(WNK4)已被证明与癌症进展密切相关。然而,它在胃癌(GC)中的参与还不清楚。本研究旨在探讨 WNK4 在胃癌中的调控机制。定量 RT-PCR 和免疫印迹显示,WNK4 在 GC 中表达下调,而 WNK4 的低表达与预后不良密切相关。包括细胞计数试剂盒-8测定和集落形成测定在内的功能测试表明,WNK4的过表达会导致体外和体内肿瘤增殖受限,而WNK4的降低则会导致相反的结果。基因组富集分析(Gene Set Enrichment Analysis,GSEA)表明,WNK4 与转录信号转导和激活因子(STAT3)之间存在潜在联系。WNK4 抑制了 GC 细胞中信号转导和转录激活因子 3(p-STAT3)的磷酸化。用Stattic抑制STAT3通路可逆转WNK4敲除诱导的GC细胞生长和增殖。这些发现为将来确定 GC 的关键治疗靶点提供了新的见解。
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引用次数: 0
Circular RNA IARS modulates the progression and ferroptosis of osteosarcoma via sponging miR-188-5p from RAB14. 环状 RNA IARS 通过从 RAB14 海绵化 miR-188-5p 调节骨肉瘤的进展和铁变态反应。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_240312N111
Yafei Li, Yan Zhang, Xiaohong Lu, Ruie Li, Jiayu Peng, Yangbo Xu

Osteosarcoma (OS) is a common primary bone tumor in children and adolescents. Circular RNA (circRNA)-IARS acts as an oncogene in multiple human tumors. However, the circ-IARS function in OS is unclear. This research aimed to elucidate the roles and mechanisms of circ-IARS in OS. In this study, circ-IARS expressions were raised in OS tissues and cells. circ-IARS expressions were closely related to clinical stage and distant metastasis. Furthermore, overall survival rates were reduced in OS patients with high circ-IARS levels. Also, silencing circ-IARS weakened OS cell proliferation and invasion, yet enhanced cell ferroptosis. Mechanistically, circ-IARS targeted miR-188-5p to regulate RAB14 expressions in OS cells. Moreover, circ-IARS knockdown repressed OS cell proliferation, invasion, and induced ferroptosis, yet these impacts were abolished by co-transfection with anti-miR-188-5p or pcDNA-RAB14. Meanwhile, interference with circ-IARS reduced OS cell proliferation, and decreased RAB14 (a member of the RAS oncogene family), GPX4, and xCT (crucial ferroptosis regulators) expressions in vivo. In conclusion, circ-IARS facilitated OS progression via miR-188-5p/RAB14.

骨肉瘤(Osteosarcoma,OS)是儿童和青少年中常见的原发性骨肿瘤。环状 RNA(circRNA)-IARS 是多种人类肿瘤的致癌基因。然而,circ-IARS在OS中的功能尚不清楚。本研究旨在阐明circ-IARS在OS中的作用和机制。该研究发现,circ-IARS在OS组织和细胞中的表达升高,circ-IARS的表达与临床分期和远处转移密切相关。此外,高circ-IARS水平的OS患者总生存率降低。同时,沉默circ-IARS会减弱OS细胞的增殖和侵袭,但会增强细胞的铁变态反应。从机理上讲,circ-IARS靶向miR-188-5p调节OS细胞中RAB14的表达。此外,circ-IARS敲除抑制了OS细胞的增殖和侵袭,并诱导了铁凋亡,而与抗miR-188-5p或pcDNA-RAB14联合转染则可消除这些影响。同时,干扰circ-IARS可减少OS细胞的增殖,降低RAB14(RAS癌基因家族成员)、GPX4和xCT(重要的铁变态调节因子)在体内的表达。总之,circ-IARS通过miR-188-5p/RAB14促进了OS的进展。
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引用次数: 0
Silencing of lncRNA LOC105376794 promotes migration, invasion, and Gefitinib resistance of lung adenocarcinoma cells with EGFR 19Del mutation by ATF4/CHOP axis and ERK phosphorylation. 沉默lncRNA LOC105376794可通过ATF4/CHOP轴和ERK磷酸化促进表皮生长因子受体19Del突变的肺腺癌细胞的迁移、侵袭和吉非替尼耐药性。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_230616N316
Wenjing Liu, Zhipeng Duan, Yefeng Wu, Rui Ma

Epidermal growth factor receptor (EGFR) gene exon 19 in-frame deletion (19del) and exon 21 L858R point mutation (21L858R mutation) are prevalent mutations in lung adenocarcinoma. Lung adenocarcinoma patients with 19del presented with a better prognosis than the 21L858R mutation under the same epidermal growth factor receptor tyrosine kinase inhibitor treatment. Our study aimed to uncover the expression of long non-coding RNA LOC105376794 between 19del and 21L858R mutation, and explore the mechanism that regulates cells' biological behavior and gefitinib sensitivity in lung adenocarcinoma cells with 19del. Transcriptome sequencing was conducted to identify differentially expressed lncRNAs between EGFR 19del and 21L858R mutation in serum through the DNBSEQ Platform. Protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway were conducted to analyze the relationship between lncRNAs and mRNAs through STRING and Dr. TOM. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of lncRNA LOC105376794 in serum and cells. Loss-of-function experiments were used to validate the biological function and gefitinib sensitivity of LOC105376794 in lung adenocarcinoma cells. Protein levels were detected by western blotting. Through transcriptome resequencing and RT-qPCR, we found the expression levels of LOC105376794 in serum were increased in the 19del group compared with the 21L858R mutation group. Inhibition of LOC105376794 promoted proliferation, migration and invasion, and reduced apoptosis of HCC827 and PC-9 cells. The low expression of LOC105376794 reduced gefitinib sensitivity in PC-9 cells. Mechanistically, we found that the knockdown of LOC105376794 suppressed activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway and facilitated the expression of extracellular signal-regulated kinase 1/2 (ERK) phosphorylation. LOC105376794 altered cell biological behavior and gefitinib sensitivity of lung adenocarcinoma cells with 19del through the ATF4/CHOP signaling pathway and the expression of ERK phosphorylation. The results further illustrated the fact that lung adenocarcinoma patients with 19del presented with a more favorable clinical outcome and provided a theoretical basis for treatment strategy for lung adenocarcinoma patients with 19del.

表皮生长因子受体(EGFR)基因第19外显子框内缺失(19del)和第21外显子L858R点突变(21L858R突变)是肺腺癌的常见突变。在同样的表皮生长因子受体酪氨酸激酶抑制剂治疗下,19del突变的肺腺癌患者的预后比21L858R突变的患者好。我们的研究旨在揭示长非编码RNA LOC105376794在19del和21L858R突变之间的表达,并探索调节19del肺腺癌细胞生物学行为和吉非替尼敏感性的机制。通过DNBSEQ平台进行转录组测序,鉴定血清中表皮生长因子受体19del和21L858R突变之间差异表达的lncRNA。通过STRING和Dr. TOM进行蛋白-蛋白相互作用网络和京都基因组百科全书途径分析lncRNA与mRNA之间的关系。采用逆转录-定量聚合酶链反应(RT-qPCR)测定lncRNA LOC105376794在血清和细胞中的表达。功能缺失实验用于验证 LOC105376794 在肺腺癌细胞中的生物学功能和吉非替尼敏感性。蛋白水平通过蛋白印迹法检测。通过转录组重测序和 RT-qPCR,我们发现与 21L858R 突变组相比,19del 组血清中 LOC105376794 的表达水平升高。抑制 LOC105376794 可促进 HCC827 和 PC-9 细胞的增殖、迁移和侵袭,并减少其凋亡。LOC105376794的低表达降低了PC-9细胞对吉非替尼的敏感性。从机理上讲,我们发现LOC105376794的敲除抑制了激活转录因子4(ATF4)/C/EBP同源蛋白(CHOP)信号通路,促进了细胞外信号调节激酶1/2(ERK)磷酸化的表达。LOC105376794通过ATF4/CHOP信号通路和ERK磷酸化表达改变了19del肺腺癌细胞的生物学行为和吉非替尼敏感性。研究结果进一步说明,19del基因肺腺癌患者的临床预后更佳,为19del基因肺腺癌患者的治疗策略提供了理论依据。
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引用次数: 0
Efficacy and safety analysis of anlotinib in combination with immune checkpoint inhibitors for second-line and subsequent extensive-stage small-cell lung cancer. 安罗替尼联合免疫检查点抑制剂治疗二线及后续广泛期小细胞肺癌的疗效和安全性分析。
IF 4.6 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_231104N572
Xixi Ying, Zheng Shi, Rongjun Shao, Guangxian You, Zhengbo Song

Currently, there is a lack of effective second-line and subsequent treatments for patients with extensive-stage small-cell lung cancer (ES-SCLC), and the establishment of a standardized treatment protocol is still underway. Considering the potential synergistic therapeutic effects of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs), combination therapy could be a viable option for treating lung cancer. This research concentrates on assessing the efficacy and safety of anlotinib in combination with ICIs for the treatment of ES-SCLC. We undertook a retrospective analysis of patients with extensive-stage SCLC who received anlotinib in combination with ICIs as second-line and subsequent treatment at Zhejiang Cancer Hospital between April 2020 and April 2023. Survival rates were analyzed using the Kaplan-Meier method. Among the 43 patients who received combination therapy, there were no cases of complete response (CR), 16 patients who achieved partial response (PR), 21 patients who had stable disease (SD), and 6 patients who experienced disease progression (PD). This resulted in an overall response rate (ORR) of 37.2% (16/43) and a disease control rate (DCR) of 86.0% (34/43). The median progression-free survival (PFS) was 4.0 months (95% CI: 2.74-5.26), and the median overall survival (OS) time was 10 months (95% CI: 4.8-15.2). Cox multifactorial regression analysis disclosed that the performance score (PS) and the number of metastatic organs were independent factors influencing PFS in ES-SCLC (p<0.001). The combination therapy demonstrated acceptable toxicity, with a total grade 3/4 toxicity rate of 30.2%. The combination therapy showed a notable association with several adverse events, including hand-foot syndrome, hypertension, and fatigue, which were the most significant. Combining anlotinib with immune checkpoint inhibitors has demonstrated favorable efficacy and safety in the treatment of second-line and subsequent extensive-stage small-cell lung cancer.

目前,广泛期小细胞肺癌(ES-SCLC)患者缺乏有效的二线治疗和后续治疗方法,标准化治疗方案的建立仍在进行中。考虑到抗血管生成药物和免疫检查点抑制剂(ICIs)的潜在协同治疗效果,联合疗法可能是治疗肺癌的一种可行选择。本研究主要评估安罗替尼联合 ICIs 治疗 ES-SCLC 的有效性和安全性。我们对2020年4月至2023年4月期间在浙江省肿瘤医院接受安罗替尼联合ICIs二线及后续治疗的广泛期SCLC患者进行了回顾性分析。生存率采用卡普兰-梅耶法进行分析。在接受联合治疗的43例患者中,没有完全应答(CR)病例,16例患者获得部分应答(PR),21例患者病情稳定(SD),6例患者病情进展(PD)。总反应率(ORR)为 37.2%(16/43),疾病控制率(DCR)为 86.0%(34/43)。中位无进展生存期(PFS)为4.0个月(95% CI:2.74-5.26),中位总生存期(OS)为10个月(95% CI:4.8-15.2)。Cox多因素回归分析显示,表现评分(PS)和转移器官数量是影响ES-SCLC患者PFS的独立因素(p
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引用次数: 0
NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells. NEK2 促进 TP53 泛素化,从而增强 TP53 野生型胶质母细胞瘤细胞的增殖和迁移。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.4149/neo_2024_240226N80
Yu Zhang, Hao Yu, Mengyao He, Wenchao Liu, Shengyou Xiao, Xiangting Wang, Ping Huang, Qiang Huang

The most common primary malignant tumor in the adult brain is glioblastoma multiforme (GBM); however, its underlying pathogenic mechanism remains elusive. The never in mitosis (NIMA)-related kinase 2 (NEK2) has been closely associated with the prognosis of various malignancies. Nevertheless, the complete elucidation of NEK2's potential clinical value, particularly in glioma prognosis and development, remains lacking. U87MG and A172 glioblastoma cells were infected with sh-NEK2 lentivirus or oe-NEK2 plasmid to investigate the effect of NEK2 on cell proliferation, migration, and invasion. Cell viability was measured using CCK-8 and colony formation assays, while Transwell assay was utilized to assess cell migration and invasion. Protein expression levels were determined through western blot analysis. Additionally, CGGA and TCGA databases were used for bioinformatics analysis in order to examine the NEK2 expression. Through comprehensive bioinformatics analysis, we identified elevated mRNA expression levels of NEK2 in gliomas compared to normal tissues, which correlated with poor prognosis among glioma patients. Moreover, functional experiments revealed that silencing NEK2 suppressed glioma cell proliferation while overexpression of NEK2 promoted migration and invasion capabilities. Finally, our study uncovered that NEK2 regulates the malignant progression of TP53 wild-type glioblastoma by facilitating TP53 ubiquitination.

多形性胶质母细胞瘤(GBM)是成人脑部最常见的原发性恶性肿瘤,但其潜在的致病机制仍难以捉摸。与有丝分裂(NIMA)相关的激酶 2(NEK2)与各种恶性肿瘤的预后密切相关。然而,NEK2的潜在临床价值,尤其是在胶质瘤预后和发展中的潜在临床价值,仍然缺乏完整的阐释。用 sh-NEK2 慢病毒或 oe-NEK2 质粒感染 U87MG 和 A172 胶质母细胞瘤细胞,研究 NEK2 对细胞增殖、迁移和侵袭的影响。细胞活力用 CCK-8 和菌落形成试验测定,细胞迁移和侵袭用 Transwell 试验评估。蛋白质表达水平通过蛋白印迹分析确定。此外,还使用 CGGA 和 TCGA 数据库进行生物信息学分析,以检测 NEK2 的表达。通过全面的生物信息学分析,我们发现与正常组织相比,神经胶质瘤中 NEK2 的 mRNA 表达水平升高,这与神经胶质瘤患者的不良预后相关。此外,功能实验显示,沉默 NEK2 可抑制胶质瘤细胞的增殖,而过表达 NEK2 则可促进细胞的迁移和侵袭能力。最后,我们的研究发现,NEK2通过促进TP53泛素化来调控TP53野生型胶质母细胞瘤的恶性进展。
{"title":"NEK2 promotes TP53 ubiquitination to enhance the proliferation and migration of TP53 wild-type glioblastoma cells.","authors":"Yu Zhang, Hao Yu, Mengyao He, Wenchao Liu, Shengyou Xiao, Xiangting Wang, Ping Huang, Qiang Huang","doi":"10.4149/neo_2024_240226N80","DOIUrl":"10.4149/neo_2024_240226N80","url":null,"abstract":"<p><p>The most common primary malignant tumor in the adult brain is glioblastoma multiforme (GBM); however, its underlying pathogenic mechanism remains elusive. The never in mitosis (NIMA)-related kinase 2 (NEK2) has been closely associated with the prognosis of various malignancies. Nevertheless, the complete elucidation of NEK2's potential clinical value, particularly in glioma prognosis and development, remains lacking. U87MG and A172 glioblastoma cells were infected with sh-NEK2 lentivirus or oe-NEK2 plasmid to investigate the effect of NEK2 on cell proliferation, migration, and invasion. Cell viability was measured using CCK-8 and colony formation assays, while Transwell assay was utilized to assess cell migration and invasion. Protein expression levels were determined through western blot analysis. Additionally, CGGA and TCGA databases were used for bioinformatics analysis in order to examine the NEK2 expression. Through comprehensive bioinformatics analysis, we identified elevated mRNA expression levels of NEK2 in gliomas compared to normal tissues, which correlated with poor prognosis among glioma patients. Moreover, functional experiments revealed that silencing NEK2 suppressed glioma cell proliferation while overexpression of NEK2 promoted migration and invasion capabilities. Finally, our study uncovered that NEK2 regulates the malignant progression of TP53 wild-type glioblastoma by facilitating TP53 ubiquitination.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":" ","pages":"255-265"},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oncogenic DDX46 promotes pancreatic cancer development and gemcitabine resistance by facilitating the JMJD6/CDK4 signaling pathway. 致癌物质DDX46通过促进JMJD6/CDK4信号通路,促进胰腺癌的发展和吉西他滨耐药性的产生。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-17 DOI: 10.4149/neo_2024_230904N469
Guang Yang, Yun Wang, Kairui Wang, Xinjia Liu, Jing Yang

Pancreatic cancer (PAAD) is a fatal malignancy with a poor prognosis. The treatment strategies are quite limited and gemcitabine is the canonical one, which has been proven to improve the prognosis of PAAD patients. However, the treatment efficiency of gemcitabine is far from satisfactory and remains to be further improved. DEAD-Box Helicase 46 (DDX46) is a kind of RNA helicase, which promotes multiple cancers development. However, its role in PAAD is largely unknown. In the present study, we found DDX46 was highly expressed in PAAD tissues and correlated with poor prognosis. Knockdown of DDX46 repressed PAAD cell growth in vitro and in vivo and sensitized PAAD cells to gemcitabine treatment. Mechanically, DDX46 bound to JMJD6 and promoted JMJD6/CDK4 signaling pathway. Overexpression of JMJD6 reversed the anti-tumor function of DDX46 knockdown. Our study found a novel pathological mechanism of PAAD progression and provided a potential therapeutic target to improve gemcitabine efficiency.

胰腺癌(PAAD)是一种预后不良的致命恶性肿瘤。目前的治疗策略非常有限,而吉西他滨是一种典型的治疗药物,已被证实可以改善胰腺癌患者的预后。然而,吉西他滨的治疗效果远不能令人满意,仍有待进一步提高。DEAD-Box螺旋酶46(DDX46)是一种RNA螺旋酶,可促进多种癌症的发展。然而,它在PAAD中的作用却鲜为人知。本研究发现,DDX46在PAAD组织中高表达,并与不良预后相关。敲除DDX46可抑制PAAD细胞在体外和体内的生长,并使PAAD细胞对吉西他滨治疗敏感。在机制上,DDX46与JMJD6结合并促进JMJD6/CDK4信号通路。JMJD6的过表达逆转了DDX46敲除的抗肿瘤功能。我们的研究发现了PAAD进展的新病理机制,并为提高吉西他滨疗效提供了潜在的治疗靶点。
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引用次数: 0
ARTN-GFRA3 axis induces epithelial-mesenchymal transition phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling. ARTN-GFRA3 轴通过 KRAS 信号诱导胃癌细胞的上皮-间质转化表型、迁移和侵袭。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_231006N524
Xiao-Long Wang, Gui-Xiu Jin, Xiao-Qiang Dong

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

神经侵犯是胃癌局部扩散的基础,与预后不良有关。近年来,这一过程受到越来越多的关注。然而,神经侵袭与胃癌细胞恶性表型之间的关系以及参与这一过程的分子机制仍不清楚。本研究利用癌症基因组图谱-胃腺癌数据集进行了生物信息学分析。结果显示,GDNF家族受体α3(GFRA3)的高表达与胃癌患者的不良预后有关。GFRA3是一种神经胶质细胞系衍生神经营养因子(GDNF)--青蒿素(ARTN)的受体。这种关联表现为总生存期/无病生存期短,以及存在高分期和高级别疾病。基因组富集分析表明,当胃癌中 GFRA3 高表达时,两个癌症相关通路(即 KRAS 信号转导和上皮-间质转化(EMT))被激活。进一步的研究证实,GFRA3 可激活 KRAS 下游信号磷脂酰肌醇 3 激酶/蛋白激酶 B(PI3K/AKT)或细胞外信号调节激酶(ERK),诱导 EMT 标志物,并促进胃癌细胞的迁移和侵袭。作为GFRA3的配体,ARTN通过GFRA3诱导胃癌细胞的EMT、迁移和侵袭。值得注意的是,ARTN-GFRA3 轴的作用会因 KRAS 抑制剂的治疗而减弱。本研究结果表明,在胃癌的神经侵袭过程中,ARTN 介导的 GFRA3 激活可通过 KRAS 信号诱导胃癌细胞的 EMT 表型、迁移和侵袭。
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引用次数: 0
Allicin inhibits the growth of HONE-1 and HNE1 human nasopharyngeal carcinoma cells by inducing ferroptosis. 大蒜素通过诱导铁变态反应抑制 HONE-1 和 HNE1 人鼻咽癌细胞的生长。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_240108N8
Xin Li, Jin-Que Luo, Xue-Qi Liao, Shuo Zhang, Li-Fan Yang, Tao Wu, Ling Wang, Qing Xu, Bin-Sheng He, Zhen Guo

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.

大蒜素(ALlicin,AL)是大蒜提取的有机硫化物之一,具有多种药理作用。研究报告显示,大蒜素对肝癌、胃癌、乳腺癌和其他癌症有显著的抑制作用。不过,目前还没有关于其在人类鼻咽癌中作用的相关报道。铁凋亡是一种非凋亡调节细胞死亡的铁依赖形式。越来越多的证据表明,诱导铁凋亡可抑制各种癌细胞的增殖、迁移、侵袭和存活,在癌症中起到抑瘤作用。本研究证实,AL 可抑制人鼻咽癌细胞的增殖、迁移、侵袭和存活。我们的研究结果表明,AL 可通过降低 GSH 和 GPX4 的水平,促进毒性 LPO 和 ROS 的诱导,从而诱导铁变态轴。AL 介导的人鼻咽癌细胞毒性依赖于铁变态反应。因此,AL 具有良好的抗癌特性,有望成为治疗鼻咽癌的潜在药物。
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引用次数: 0
Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma. 多种原发性癌症对肝细胞癌患者总生存期的影响。
IF 2 4区 医学 Q3 ONCOLOGY Pub Date : 2024-06-01 DOI: 10.4149/neo_2024_231217N649
Petr Hříbek, Sona Fraňková, Johana Klasová, Klára Chmelová, Lucie Miková, Jan Šperl, Petr Urbánek

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

多原发癌(MPC)的发病率不断上升是一个长期趋势,但肝细胞癌(HCC)患者中MPC的发病率及其对总生存期(OS)的影响仍是未知数。我们对在两个三级中心接受治疗的 497 例 HCC 患者进行了回顾性分析。该群体被分为两个亚组--肝移植(LT,324 例患者)和非肝移植(非 LT,173 例患者)。我们分析了MPC的发生、对生存的影响,并确定了预测不利结果的变量。88名患者(18%)检测出了多发性骨髓瘤。最常见的MPC是前列腺癌(17%)、皮肤癌(15.9%)、肾癌(12.5%)和肺癌(10.2%)。全组、LT 和非 LT 亚组的中位 OS 分别为 70、116 和 17 个月(P<0.05)。
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