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常珂;吴婷婷;张思棋;杨帆;任春霞;余自成 《生命的化学》2024,(4):736-748
为探讨铁死亡基因溶质载体家族7成员11(SLC7A11)与肺腺癌(lung adenocarcinoma,LUAD)表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKIs)埃克替尼(Icotinib,Ico)耐药的相关性,借助数据库分析SLC7A11在肺腺组织与肺腺癌组织的表达差异,分析SLC7A11与肺腺癌患者临床分期和生存率的相关性,并分析SLC7A11与谷胱甘肽过氧化物酶4(GPX4)、血红素加氧酶-1(HO-1)、核因子E2相关因子2(Nrf2)、转铁蛋白(transferrin)以及EGFR之间的蛋白互作网络(PPI)。通过实时荧光定量PCR(qPCR)、蛋白质免疫印迹(Western blot)和细胞活力测量试剂盒(CCK-8实验)检测肺腺癌细胞系H1975与PC-9细胞铁死亡基因的表达差异及其对埃克替尼的敏感性差异。通过建立基因SLC7A11过表达和敲低的细胞模型,分析基因SLC7A11对肺腺癌埃克替尼敏感性的影响。结果发现,SLC7A11在包括肺腺癌在内的多种癌症组织中高表达,且SLC7A11的表达水平与肺腺癌患者的疾病进展密切相关,高表达SLC7A11的肺腺癌患者预后较差。H1975细胞对埃克替尼的敏感性显著低于PC-9细胞,且H1975细胞的铁死亡相关基因Nrf2、GPX4和HO-1在mRNA水平显著上调;Western blot实验结果进一步证实,H1975细胞GPX4、HO-1和SLC7A11在蛋白质水平显著上调。过表达SLC7A11的PC-9细胞对埃克替尼的敏感性显著降低并且对抗其诱导的铁死亡的发生。相反,敲低SLC7A11的H1975细胞对埃克替尼的敏感性显著增加,并可促进其诱导的铁死亡的发生。结果表明,基因SLC7A11在肺腺癌埃克替尼耐药中起着重要作用,可以通过调控SLC7A11诱导铁死亡增强肺腺癌对埃克替尼的敏感性。 相似文献
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为探讨热休克蛋白70(heatshockprotein70,HSP70)在肺腺癌中的表达及其作用,首先采用免疫印迹检测经临床支纤镜确诊并行手术切除的肺腺癌组织标本中HSP70的表达,结果显示在癌旁正常组织中HSP70的表达量显著低于其在癌组织中的表达量.其次,采用HSP70反义寡核苷酸阻断A549细胞中HSP70表达后,经MTT和Hoechst33258检测发现,HSP70下调能显著促进放线菌素D(actinomycinD,ActD)所致的A549细胞增殖抑制及凋亡,反义寡核苷酸处理组与正义或随机寡核苷酸处理组比较P值均小于0.05.进一步构建HSP70真核重组质粒并瞬时转染A549细胞后,能显著增加A549细胞中HSP70表达,同时采用MTT和流式细胞术及基因组DNA琼脂糖凝胶电泳检测发现,HSP70过表达能显著抵消ActD所致细胞增殖抑制及凋亡,转染HSP70重组质粒组与转染空载体组相比P值小于0.05.上述结果提示,HSP70在肺腺癌组织中高表达,高表达的HSP70在降低肺腺癌细胞对ActD的敏感性及促进癌细胞增殖与抑制凋亡等方面发挥了重要作用. 相似文献
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目的: 探讨低氧促进肺腺癌A549细胞迁移的机制。方法: 培养肺腺癌A549细胞,转染慢病毒获得稳定敲低ACC1的A549细胞株,转染si-RNA获得敲低SREBP-1的A549细胞。分别以低氧(5％ O2)联合低氧诱导因子1α(HIF-1α)抑制剂PX-478(25 μmol)处理A549细胞,低氧联合亚油酸(LA)(20 μmol)处理敲低ACC1的A549细胞,低氧处理敲低胆固醇调节原件结合蛋白1(SREBP-1)的A549细胞。Transwell实验检测细胞迁移,蛋白质印迹法检测HIF-1α、ACC1及上皮-间质转化(EMT)相关波形蛋白(Vimentin)及E-钙黏蛋白(E-Cadherin)的表达与SREBP-1的表达,实时荧光定量聚合酶链反应(RT-qPCR)检测低氧联合HIF-1α抑制剂PX-478(25 μmol)处理A549细胞后ACC1及SREBP-1 mRNA水平变化。每项实验重复三次。结果: 与常氧组相比,低氧组A549细胞迁移数增加,ACC1与HIF-1α表达上调(P均＜0.01),SREBP-1表达上调(P＜0.05);与低氧对照组相比,PX-478(25 μmol)抑制A549细胞迁移,SREBP-1表达下调(P＜0.05);低氧处理A549细胞后ACC1 mRNA上升(P＜0.05),SREBP-1 mRNA水平上升(P＜0.01);低氧并使用PX-478(25 μmol)处理A549细胞24 h,ACC1 mRNA水平下降(P＜0.05),SREBP-1 mRNA 水平下降(P＜0.01);转染si-RNA获得敲低SREBP-1的A549细胞,Transwell 实验显示si-SREBP-1组细胞迁移数较常氧对照组减少(P＜0.01);低氧处理si-SREBP-1组与si-NC组,与对照组相比si-SREBP-1组细胞迁移数减少(P＜0.01)但与常氧组相比差异无统计学意义(P＞0.05);Western blot检测到si-SREBP-1组ACC1表达较对照组下降(P＜0.01);低氧处理si-SREBP-1组,ACC1表达较对照组下降(P＜0.01);敲低ACC1抑制A549细胞迁移(P＜0.05),敲低ACC1后A549细胞在常氧和5％ O2条件下细胞迁移数目差异无统计学意义(P＞ 0.05);低氧处理敲低ACC1的A549细胞并给予LA(25 μmol)促进A549细胞迁移(P＜0.05)。结论: 低氧通过HIF-1α/SREBP-1/ACC1途径调节脂肪酸代谢进而促进肺腺癌A549细胞迁移。 相似文献
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哺乳动物TULP家族成员包含TUB、TULP1、TULP2、TULP3和TULP4共五种,它们在哺乳动物多种组织中表达,与个体的生长发育、稳态维系、遗传及基因突变所致疾病关系密切。近年来对TULP家族成员的生物学功能及其与疾病的相关性已进行了深入的研究,如TUB所致肥胖-听力减退-视网膜三联征;TULP1的视觉功能与相关眼病治疗方法的探索及评估改进;TULP3除了在胚胎神经发育中的作用及其突变可致纤毛病多囊肾外,更成为相关肿瘤调控的研究热点;TULP4被证明与遗传所致畸形及阿尔茨海默症有关,同时因成为多种疾病的候选基因而受到广泛关注;而TULP2在雄性生殖中的作用也得到了初步的揭示。本文对TULP家族成员在哺乳动物中的生物学功能及其变异所致疾病的发病机制进行了综述,以期为相关疾病的诊断和治疗提供理论依据。 相似文献
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细胞色素P450 (cytochrome P450, CYP450)是一类血红素氧化酶。细胞色素P450家族2亚家族R成员1（cytochrome P450 family 2 subfamily R member 1, CYP2R1）是一种主要在肝组织中表达的维生素D羟化酶。目前,对于小鼠CYP2R1蛋白质的结构、物化特性和病理机制的理了解仍十分有限。本研究结合基因克隆和生物信息学分析,获得小鼠CYP2R1基因CDS序列及其生物学特征。随后,利用pcDNA3.1-CYP2R1真核表达载体,通过细胞划痕、MTT分析、real-time qPCR方法检测异源表达CYP2R1对肺癌细胞A549、胃癌细胞7901、肝癌细胞HepG2以及正常细胞HEK293T细胞的迁移、增殖和细胞周期基因表达的影响,探明其对癌细胞增殖的作用。结果显示,由C57BL/6小鼠肝组织的CYP2R1基因,序列长度1 506 bp,其中,CDS 468 bp。其编码的155个氨基酸,与其他11个物种间的同源性均较高,其三级结构与人CYP2R1略有不同。构建的pcDNA3.1-CYP2R1真核表达载体,可在体外培养细胞中提高CYP2R1基因mRNA表达105倍以上,蛋白质水平提高约30倍。值得注意的是,异源表达CYP2R1在癌细胞增殖中的作用具有差异性,其中,CYP2R1通过显著降低细胞周期蛋白基因CyclinD1(P<0.05)和Caspase3(P<0.01),而抑制7901细胞的增殖。该研究结果为进一步探索CYP2R1的生物学作用,特别是在分析其对癌细胞增殖方面提供了基础研究数据,并为进一步明确CYP2R1在癌症相关治疗中的重要意义奠定了理论基础。 相似文献
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维甲酸信号通路在调节脊椎动物发育、细胞分化和维持组织稳态平衡中发挥重要功能。作为催化视黄醛氧化成维甲酸的关键酶,乙醛脱氢酶1家族成员A2 (aldehyde dehydrogenase 1 family member A2, Aldh1a2)在调节心脏发育过程中具有重要功能,而其在心脏疾病中发挥的功能尚不明晰。本研究通过构建和包装用于过表达Aldh1a2的腺病毒(Ad-Aldh1a2),将其感染原代心肌细胞后分析Aldh1a2过表达对心肌细胞生物学功能的影响。结果显示心肌细胞感染Ad-Aldh1a2后能够成功实现Aldh1a2的过表达;与感染Ad-GFP的对照组相比,感染Ad-Aldh1a2的心肌细胞尺寸明显增加,胚胎期基因心房利钠肽(atrial natriuretic factor, ANF)、脑利钠肽(brain natriuretic peptide, BNP)和β-肌球蛋白重链(β-myosin heavy chain, β-MHC)表达水平上调;此外,5-乙炔基-2ʹ-脱氧尿苷(EdU)掺入实验结果显示,Aldh1a2过表达使EdU掺入阳性信号的心肌细胞比例升高,检测增殖相关基因的表达发现细胞周期蛋白D2 (cycline D2, Ccnd2)和苯并咪唑出芽抑制解除同源物蛋白-1 (budding uninhibited by benzimidazole 1, Bub1)的表达水平也明显升高。以上结果表明Aldh1a2过表达可促进心肌细胞肥大生长和增殖。本研究为进一步了解Aldh1a2在心脏疾病中的功能、发展心脏疾病的治疗策略提供了有益的基础。 相似文献
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目的:探讨褪黑素(MLT)对体外培养的肺腺癌A549细胞增殖的影响及作用机制。方法:体外培养人肺腺癌A549细胞,通过不同浓度的褪黑素(0.1、1.0、2.5、5.0mmol/L)干预24、48、72h,通过噻唑蓝(MTT)法测定细胞增殖,DNA末端原位标记染色法(Tunel)检测细胞凋亡情况,蛋白印迹(Western-blot)法检测褪黑素对A549细胞核内核转录因子Bp65(NF-Bp65)蛋白水平的影响。结果:褪黑素能够抑制人肺腺癌A549细胞增殖,呈剂量、时间依赖性性;高浓度褪黑素作用后凋亡细胞比例明显升高,同时细胞核内NF-Bp65蛋白量明显减少。结论:褪黑素能够呈剂量、时间依赖性抑制人肺腺癌A549细胞的增殖,抑制核因子Bp65的核移位诱导细胞凋亡是可能作用路径之一。 相似文献
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BMP9属于TGF-β超家族的成员,参与多种细胞的增殖、分化、凋亡、侵袭、转移过程。以人肺腺癌细胞A549作为目的细胞,采用腺病毒体外感染方式,外源性高表达BMP9。RT-PCR及Westernblot检测重组细胞中BMP9的表达,通过细胞划痕实验、Transwell侵袭实验检测AdBMP9细胞侵袭及迁移改变,RT-PCR及Westernblot检测感染BMP9腺病毒后IL-6的mRNA和蛋白表达：Westemblotg检测NPI3K／Akt信号通路中总Akt和磷酸化Akt蛋白的表达。结果显示：与对照组细胞相比,感染BMP9腺病毒后,A549中BMP9mRNA和蛋白表达明显升高;实验组划痕愈合率由对照的（85．4±2．11％与（86．5±3．4）％上升至（97．4±2．6）％（P〈0．05）;实验组穿膜细胞数由对照的（115．5±13．1）个与（123．3±14．9）个上升至（224．3±24．6）个（P〈0．05）;与对照组细胞相比,AdBMP9组IL-6的表达上调,磷酸化Akt蛋白表达上调。该研究表明,BMP9可能通过上调IL-6的表达,激活P13K／Akt信号通路,促进人肺腺癌A549的侵袭、迁移。 相似文献
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In the US, lung carcinoma accounted for over 150,000 deaths in 2018 and the advances in increasing survival rates are still limited. In this study, we investigated the cohorts with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) from The Cancer Genome Atlas to figure out the risk factors and genomic alterations that affected their prognosis. The histoclinical factors that differed between LUAD and LUSC were identified and the risk factors affecting the overall survival were figured out for both LUAD and LUSC. Next, the patterns of nucleotides substitutions and the mutational signatures were extracted to illustrate whether different mutational processes performed for them. Finally, the genes that had different frequencies of mutation were identified. LUAD and LUSC presented differences in histoclinical factors including age at the time of diagnosis, sex, smoking history, pathological T classification, and overall survival. This was caused by the distinct genomic alterations including the transition-to-transversion ratios, mutational signatures, and the frequently mutated genes. We proposed that the mutational signature associated with aging could be used to predict the prognosis of patients with LUAD. On the other hand, the AID/APOBEC family was associated with the prognosis of LUSC. Finally, SNTG1 and LRRK2 might be important in LUAD and LUSC, respectively. 相似文献
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Chongyu Su Kang Shi Xu Cheng Yi Han Yunsong Li Daping Yu Zhidong Liu 《Journal of cellular physiology》2019,234(3):2954-2962
Our main objective is probing the effect of methylation of CLEC14A on its expression and lung adenocarcinoma (LUAD) progression. Microarray analysis was utilized to screen out differentially downregulated genes with hypermethylation in LUAD tissues. The CLEC14A expression level was measured by western blot analysis and qRT-PCR. Methylation-specific-PCR was performed to evaluate methylation status of CLEC14A. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromid (MTT) assay was used to check the relation between CLEC14A expression and cell proliferation. Cell cycle, cell apoptosis, migration, and invasion were respectively detected by the flow cytometry assay, wound healing assay, and transwell assay. Tumor xenograft models were established for investigating the effect of CLEC14A on tumor formation. CLEC14A expression in LUAD tissues was impaired compared with that in adjacent tissues, and CLEC14A promoter was highly methylated in LUAD. Overexpressing CLEC14A or inhibiting the methylation level of CLEC14A in A549 and LTEP-a-2 cells impeded the duplication of LUAD cells, promoted apoptosis, attenuated cell migration, and invasion ability, and arrested cell cycle at the G0/G1 phase. Overexpression of CLEC14A inhibited tumorigenesis of LUAD cells in nude mice. The promoter of CLEC14A is methylated in LUAD, leading to downregulation of CLEC14A in LUAD. CLEC14A acts as an antitumor role in LUAD by suppressing cell proliferation, migration, invasion, promoting cell apoptosis, and reducing tumorigenicity in nude mice. Thus, the inhibition of CLEC14A methylation is a novel strategy for the clinic treatment of LUAD. 相似文献
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Lung adenocarcinoma (LUAD) is a common cancer with high mortality worldwide. PANoptosis is a novel inflammatory programmed cell death modality with the characteristics of pyroptosis, apoptosis and necroptosis. It is necessary to explore PANoptosis-related genes in LUAD patients and offer evidence for prognosis prediction and therapeutic strategies. Single-cell RNA sequencing data and RNA expression profiles of LUAD patients from The Cancer Genome Atlas and Gene Expression Omnibus databases are used to screen PANoptosis-related differential genes for the construction of a risk model. Fifteen PANoptosis-related markers with prognostic value were identified by Least Absolute Shrinkage and Selection Operator (LASSO)–Cox regression analysis. Kaplan–Meier analysis and receiver operating characteristic curve analysis further demonstrated the significant predictive capability. Immune infiltration, Single Nucleotide Variants (SNV) mutations, and clinical drug susceptibility were analyzed. In conclusion, a risk model of 15 PANoptosis-related genes has significant value in prognostic prediction for LUAD and has potential to direct clinical therapeutic strategies during the treatment. 相似文献
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Lung cancer is one of the most frequently diagnosed malignant tumors and the main reason for cancer-related death around the world, whereas nonsmall cell lung cancer that consists two subtypes: lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) is responsible for an estimated 85% of all lung cancers. The current study aimed to explore gene expression and methylation differences between LUAD and LUSC. EdgeR was used to identify differentially regulated genes between normal and cancer in the LUAD and LUSC extracted from The Cancer Genome Atlas (TCGA), respectively, whereas SAM was used to find genes with differential methylation between normal and cancer in the LUAD and LUSC, respectively. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to analyze the function which these genes enriched in. A total of 391 genes with opposite methylation patterns in LUAD and LUSC and four functional pathways were obtained (false discovery rate (FDR) < 0.1). These pathways mainly included fat digestion and absorption, phenylalanine metabolism, bile secretion, and so on, which were related to the airframe nutrition metabolic pathway. Moreover, two genes CTSE (cathepsin E) and solute carrier family 5 member 7 (SLC5A7) were also found, among which CTSE was overexpressed and hypomethylated in LUAD corresponding to normal lung tissues, whereas SLC5A7 showed the opposite in LUAD. In conclusion, this study investigated the differences between the gene expression and methylation patterns in LUAD and LUSC, and explored their different biological characteristics. Further understanding of these differences may promote the discovery and development of new, accurate strategies for the prevention, diagnosis, and treatment of lung cancer. 相似文献
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Liwei Wu Zilu Wen Yanzheng Song Lin Wang 《Journal of cellular and molecular medicine》2021,25(12):5681-5690
Long non-coding RNA (lncRNA) is an important regulatory factor in the development of lung adenocarcinoma, which is related to the control of autophagy. LncRNA can also be used as a biomarker of prognosis in patients with lung adenocarcinoma. Therefore, it is important to determine the prognostic value of autophagy-related lncRNA in lung adenocarcinoma. In this study, autophagy-related mRNAs-lncRNAs were screened from lung adenocarcinoma and a co-expression network of autophagy-related mRNAs-lncRNAs was constructed by using The Cancer Genome Atlas (TCGA). The univariate and multivariate Cox proportional hazard analyses were used to evaluate the prognostic value of the autophagy-related lncRNAs and finally obtained a survival model composed of 11 autophagy-related lncRNAs. Through Kaplan-Meier analysis, univariate and multivariate Cox regression analysis and time-dependent receiver operating characteristic (ROC) curve analysis, it was further verified that the survival model was a new independent prognostic factor for patients with lung adenocarcinoma. In addition, based on the survival model, gene set enrichment analysis (GSEA) was used to illustrate the function of genes in low-risk and high-risk groups. These 11 lncRNAs were GAS6-AS1, AC106047.1, AC010980.2, AL034397.3, NKILA, AL606489.1, HLA-DQB1-AS1, LINC01116, LINC01806, FAM83A-AS1 and AC090559.1. The hazard ratio (HR) of the risk score was 1.256 (1.196-1.320) (P < .001) in univariate Cox regression analysis and 1.215 (1.149-1.286) (P < .001) in multivariate Cox regression analysis. And the AUC value of the risk score was 0.809. The 11 autophagy-related lncRNA survival models had important predictive value for the prognosis of lung adenocarcinoma and may become clinical autophagy-related therapeutic targets. 相似文献
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Liwen Zhang Miao He Wenjing Zhu Xuemei Lv Yanyun Zhao Yuanyuan Yan Xueping Li Longyang Jiang Lin Zhao Yue Fan Panpan Su Mengcong Gao Heyao Ma Kai Li Minjie Wei 《Journal of cellular physiology》2020,235(5):4361-4375
Lung adenocarcinoma (LUAD) is one of the most malignant tumor types worldwide. Our objective was to identify a genetic signature that could predict the prognosis of patients with LUAD. We extracted gene data sets from The Cancer Genome Atlas and obtained differentially expressed genes that were highly expressed at every stage. These genes were analyzed using gene set enrichment analysis to obtain four biological processes associated with LUAD. Subsequently, Cox univariate and multivariate analyses were performed to generate four optimized models (G2M checkpoint, E2F targets, mitotic spindle, and glycolysis). We identified a mitotic spindle-related signature (KIF15, BUB1, CCNB2, CDK1, KIF4A, DLGAP5, ECT2, and ANLN), which could be an independent prognostic indicator, to predict the prognosis of patients with LUAD. This new discovery should offer opportunities to explore the pathogenesis of LUAD and prove clinically useful in predicting LUAD patient prognosis. 相似文献
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FOXM1(Forkhead box protein M1)是调控细胞增殖的重要转录因子,近年来研究表明与肿瘤发生密切相关,但与卵巢癌的关系尚不明确.通过检测68例卵巢癌标本、21例卵巢良性肿瘤标本、24例正常卵巢标本以及3株卵巢癌细胞系(A2780细胞、OVCAR3细胞、SKOV3细胞)中FOXM1的表达情况,分析其与临床参数之间的相关性及临床意义.结果显示卵巢癌中FOXM1表达明显高于卵巢良性肿瘤及正常卵巢组织,差异极为显著,其中低分化细胞中表达强于中高分化细胞(P=0.013),Ⅲ～Ⅳ期表达强于Ⅰ～Ⅱ期(P=0.011),但与病理类型无关;FOXM1在3株卵巢癌细胞系中均有较强表达.FOXM1在卵巢癌组织及3种卵巢癌细胞系中存在高表达,且与卵巢癌分化程度及临床分期有关. 相似文献
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九次跨膜超家族蛋白成员1（transmembrane 9 superfamily protein member 1,TM9SF1）在进化过程中高度保守,在人体组织和多种细胞系广泛表达。目前,关于该蛋白质的功能研究十分有限和初步。本研究采用慢病毒介导的TM9SF1表达系统,研究了重组TM9SF1蛋白的生化特点及其对细胞生长的调控作用。慢病毒感染的293T全细胞裂解液的蛋白质免疫印迹结果揭示,TM9SF1蛋白具有表观分子质量约为70 kD的单体及寡聚体两种主要形式;在室温及加热37℃时蛋白质相对稳定,随变性温度升高（56 ℃以上）逐渐失去其稳定性。CCK8法显示,与慢病毒空载体感染的293T细胞比较,TM9SF1慢病毒表达载体感染的293T细胞在感染2 d后增殖明显减缓（P<0.001）。Western印迹结果证明,过表达TM9SF1引起LC3Ⅱ表达明显上调,LC3Ⅱ/LC3Ⅰ比例升高,说明TM9SF1可引起293T细胞发生自噬。荧光实时定量PCR结果显示,过表达TM9SF1的293T细胞内质网应激标志分子CHOP、GADD34和XBP1（S）表达水平是对照细胞的3～4倍,提示发生了内质网应激反应。以上结果提示,TM9SF1具有抑制293T细胞生长的功能,该功能可能与其引起的内质网应激和自噬有关。这一结论将进一步加深对TM9SF1在细胞生长调控中的功能的认识。 相似文献
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KCNJ4 (potassium voltage‐gated channel subfamily J member 4) belongs to the inward rectifier potassium channel family, which is inhibited by novel anticancer agents. However, the biologic significance of KCNJ4 in lung adenocarcinoma (LADC) is largely unknown. Therefore, in this study, we evaluated the expression, clinical correlation, and prognostic value of KCNJ4 in LADC and normal lung tissues according to data from The Cancer Genome Atlas datasets. A small interfering RNA (siRNA)‐mediated technology was used to inhibit the expression level of KCNJ4. Cell counting kit‐8 and plate colony formation assays were used to measure cell proliferation. Wound‐healing and transwell assays were applied to detect cell mobility and metastasis. Quantitative real‐time polymerase chain reaction and western blot analysis were used to examine messenger RNA and protein expressions, respectively. It was found that KCNJ4 was significantly upregulated in LADC tissues and cells. The high level of KCNJ4 predicted shorter overall survival and was identified as an independent prognostic factor in patients with LADC. siRNA‐mediated KCNJ4 silencing impeded LADC cell proliferation, migration, and invasion. Knockdown of KCNJ4 suppressed the expression of phosphorylated mitogen‐activated protein kinase/extracellular signal regulated kinase (p‐MEK) and phosphorylated extracellular signal‐regulated kinase (p‐ERK). Collectively, these results shed some light on the contribution of KCNJ4 functioning as a significant player in LADC, implying that KCNJ4 might be a valuable prognostic biomarker and a potential therapeutic target for LADC treatment. 相似文献