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miR-627-3p并发靶向stk11/KEAP1调控肺腺癌的铁死亡研究

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实用癌症杂志 2023年第7期38卷 1066-1070页

作者：张苗苗田君娜孙颖颖河南省南阳市中心医院 473000

目的探讨miR-627-3p调控肺腺癌铁死亡的潜在机制。方法纳入肺腺癌患者126例,收集肺腺癌组织和癌旁组织后使用miRNA微阵列检测差异miRNA并分析miRNA与肺腺癌患者生存率的相关性。过表达或敲低miRNA后检测肺腺癌细胞Calu-3的增殖水平和铁... 详细信息

目的探讨miR-627-3p调控肺腺癌铁死亡的潜在机制。方法纳入肺腺癌患者126例,收集肺腺癌组织和癌旁组织后使用miRNA微阵列检测差异miRNA并分析miRNA与肺腺癌患者生存率的相关性。过表达或敲低miRNA后检测肺腺癌细胞Calu-3的增殖水平和铁死亡水平。使用miRDB数据库分析miR-627-3p发挥生物学功能的潜在底物,选取评分最高的60个基因进行siRNA敲低筛选以鉴定miR-627-3p的底物。结果miRNA微阵列分析发现有27种miRNA变化显著,其中14种miRNA在肺腺癌组织中表达下调,13种miRNA在肺腺癌组织中表达上调。其中,miR-627-3p高表达的肺腺癌患者生存率优于miR-627-3p低表达的肺腺癌患者。过表达miR-627-3p后,肺腺癌细胞Calu-3的细胞增殖水平下降(Pstk11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平下降(Pstk11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平上升(Pstk11或KEAP1的mRNA和蛋白水平下降;敲低miR-627-3p后,肺腺癌细胞Calu-3中stk11或KEAP1的mRNA和蛋白水平上升。此外,miR-627-3p结合stk11或KEAP1的3'端非翻译区。结论miR-627-3p通过并发靶向stk11/KEAP1促进肺腺癌的铁死亡水平。miR-627-3p可能是治疗肺腺癌的有用治疗靶点。

关键词： miR-627-3p stk11 KEAP1 肺腺癌铁死亡

stk11基因突变与非小细胞肺癌免疫治疗相关性研究进展

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肿瘤防治研究 2022年第8期49卷 850-854页

作者：夏思雨赵梓彤李里哈尔滨医科大学附属第二医院肿瘤内科二病房哈尔滨150086

肺癌是最常见的恶性肿瘤之一。在全球范围内,肺癌的发病率及死亡率都极高且呈上升趋势。近年来,免疫检查点抑制剂(ICIs)在晚期非小细胞型肺癌治疗中产生了显著的生存优势,然而对于驱动基因阳性的非小细胞肺癌患者,免疫检查点抑制剂疗效... 详细信息

肺癌是最常见的恶性肿瘤之一。在全球范围内,肺癌的发病率及死亡率都极高且呈上升趋势。近年来,免疫检查点抑制剂(ICIs)在晚期非小细胞型肺癌治疗中产生了显著的生存优势,然而对于驱动基因阳性的非小细胞肺癌患者,免疫检查点抑制剂疗效不佳。但一些抑癌基因可以通过突变或缺失等方式对免疫治疗产生不同程度的影响,其中丝氨酸/苏氨酸激酶11(stk11)基因突变与PD-1/PD-L1免疫检查点抑制剂有效性密切相关,研究发现stk11突变与免疫细胞浸润减少、PD-L1低表达和对PD-L1抑制反应差有关。本文就非小细胞肺癌中stk11基因突变与免疫治疗相关性的研究进展作一综述。

关键词： stk11 免疫检查点抑制剂非小细胞肺癌基因突变免疫治疗

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构建stk11基因融合质粒检测其对肺癌细胞迁移能力的影响

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肿瘤防治研究 2014年第7期41卷 707-710页

作者：张鑫君邱祥南章龙珍王建设丁昕辛勇覃朝晖姚元虎徐州医学院附属医院放射治疗科徐州医学院肿瘤生物治疗实验室江苏徐州221002

目的构建表达stk11(serine/threonine kinase 11,stk11)基因和报告基因EGFP融合蛋白的重组质粒,并转染肺癌A549和H460细胞株,检测其对肺癌细胞迁移能力的影响。方法构建重组质粒pEGFP-stk11,双酶切和测序进行鉴定。重组质粒转染A549和H... 详细信息

目的构建表达stk11(serine/threonine kinase 11,stk11)基因和报告基因EGFP融合蛋白的重组质粒,并转染肺癌A549和H460细胞株,检测其对肺癌细胞迁移能力的影响。方法构建重组质粒pEGFP-stk11,双酶切和测序进行鉴定。重组质粒转染A549和H460细胞株,荧光显微镜观察EGFP蛋白表达情况,Western blot检测stk11蛋白表达情况,划痕实验检测其对肺癌细胞迁移能力的影响。结果酶切和测序结果表明pEGFP-stk11重组质粒构建成功;在转染A549和H460细胞后24h观察到绿色荧光最强;Western blot结果显示stk11蛋白在转染后24 h条带最深;划痕实验显示,转染组细胞迁移距离小于0.9%氯化钠溶液对照组(Pstk11基因重组质粒,并能转染A549和H460细胞,转染后对肺癌细胞迁移能力起一定抑制作用。

关键词： stk11 细胞迁移 A549 H460

Peutz-Jeghers综合征基因型研究及临床诊治进展

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中华结直肠疾病电子杂志 2024年第1期13卷 6-13页

作者：张智董志伟徐祖鑫姜莉鑫张玉辉顾国利中国人民解放军空军特色医学中心普通外科北京100142 安徽医科大学第五临床学院合肥230032 中国医科大学研究生院沈阳110122

Peutz-Jeghers综合征(PJS)是一种临床罕见的常染色体显性遗传病,该病以皮肤黏膜色素斑、胃肠道多发错构瘤息肉和家族遗传性为特征性临床表现,其罹患恶性肿瘤的发生率明显高于正常人群。该病的分子发病机制与抑癌基因stk11功能异常相关,... 详细信息

Peutz-Jeghers综合征(PJS)是一种临床罕见的常染色体显性遗传病,该病以皮肤黏膜色素斑、胃肠道多发错构瘤息肉和家族遗传性为特征性临床表现,其罹患恶性肿瘤的发生率明显高于正常人群。该病的分子发病机制与抑癌基因stk11功能异常相关,但其遗传学背景复杂,临床异质性明显。目前的治疗以消化内镜的镜下治疗为主,辅之以外科手术,可显著延长患者的生存期,但尚无根治性的手段。本文复习了关于该病的相关文献,对其遗传学特性和临床治疗进展进行综述,并对未来的研究方向进行展望。

关键词：遗传性疾病基因型 Peutz-Jeghers综合征临床表型 stk11

Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome

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World Journal of Gastroenterology 2020年第16期26卷 1926-1937页

作者： Zhi Zhang Fu-Xiao Duan Guo-Li Gu Peng-Fei Yu Air Force Clinical College(Air Force Medical Center)of Anhui Medical University Beijing 100142China Department of General Surgery the General Hospital of Northern Theater Command PLAShenyang 110016Liaoning ProvinceChina Department of General Surgery Air Force Medical CenterPLABeijing 100142China

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to *** clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still *** To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of *** Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and *** hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/stk11 gene sequencing using next-generation sequencing *** correlations between the sequencing results and clinical pathological data of PJS were *** Fourteen types of LKB1/stk11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1G>T,c.464+1G>A,and c.598-1G>A);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/*** these,MSH2:c.792+1G>A,MSH6:c.3689C>G,c.4001+13C>CTTAC,PMS1:c.46C>t,and c.922G>A were new *** The genetic mutations in hamartoma polyp tissue of PJS are complex and ***,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/stk11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/stk11 mutations were larger in diameter than those with other gene mutations.

关键词： Peutz-Jeghers syndrome stk11 gene LKB1 gene Sequencing Genetic analysis

Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome

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World Journal of Gastroenterology 2021年第39期27卷 6631-6646页

作者： Guo-Li Gu Zhi Zhang Yu-Hui Zhang Peng-Fei Yu Zhi-Wei Dong Hai-Rui Yang Ying Yuan Department of General Surgery Air Force Medical CenterChinese People's Liberation ArmyBeijing 100142China Graduate School Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Department of Medical Oncology Cancer InstituteThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009Zhejiang ProvinceChina

Different types of pathogenic mutations may produce different clinical phenotypes,but a correlation between Peutz-Jeghers syndrome(PJS)genotype and clinical phenotype has not been *** all patients with PJS have detectable mutations of the stk11/LKB1 gene,what is the genetic basis of clinical phenotypic heterogeneity of PJS?Do PJS cases without stk11/LKB1 mutations have other pathogenic genes?Those are clinical problems that perplex *** The aim was to investigate the specific gene mutation of PJS,and the correlation between the genotype and clinical phenotype of *** A total of 24 patients with PJS admitted to the Air Force Medical Center,PLA(formerly the Air Force General Hospital,PLA)from November 1994 to January 2020 were randomly selected for inclusion in the *** hundred thirty-nine common hereditary tumor-related genes including stk11/LKB1 were screened and analyzed for pathogenic germline mutations by high-throughput nextgeneration sequencing(NGS).The mutation status of the genes and their relationship with clinical phenotypes of PJS were *** Twenty of the 24 PJS patients in this group(83.3%)had stk11/LKB1 gene mutations,90%of which were pathogenic mutations,and ten had new mutation *** mutations in exon 7 of stk11/LKB1 gene were significantly lower than in other *** mutations are more common in exons 1 and 4 of stk11/LKB1,and their pathogenicity was significantly higher than that of missense *** also found SLX4 gene mutations in PJS *** PJS has a relatively complicated genetic *** in the sites responsible for coding functional proteins in exon 1 and exon 4 of stk11/LKB1 may be one of the main causes of *** of the SLX4 gene may be a cause of genetic heterogeneity in PJS.

关键词： Peutz-Jeghers syndrome Genotype Phenotype stk11 Mutation

Clinical features,diagnosis,and treatment of Peutz-Jeghers syndrome:Experience with 566 Chinese cases

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World Journal of Gastroenterology 2023年第10期29卷 1627-1637页

作者： Zu-Xin Xu Li-Xin Jiang Yu-Rui Chen Yu-Hui Zhang Zhi Zhang Peng-Fei Yu Zhi-Wei Dong Hai-Rui Yang Guo-Li Gu Fifth Clinical College of Anhui Medical University Air Force Clinical College of Anhui Medical UniversityBeijing 100142China Air Force Clinical College of China Medical University Beijing 100142China Department of General Surgery Air Force Medical CenterChinese People's Liberation ArmyBeijing 100142China

BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical *** preventive and curative methods are still *** we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features,diagnosis,and *** To explore the clinical features,diagnosis,and treatment of PJS in a Chinese medical *** The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized.A clinical database was established covering age,gender,ethnicity,family history,age at first treatment,time and sequence of appearance of mucocutaneous pigmentation,polyp distribution,quantity,and diameter,frequency of hospitalization,fre-quency of surgical operations,*** clinical data was retrospectively analyzed using SPSS 26.0 software,with P<0.05 considered statistically *** Of all the patients included,55.3%were male and 44.7%were *** time to the appearance of mucocutaneous pigmentation was 2 years,and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 *** vast majority(92.2%)of patients underwent small bowel endoscopy and treatment,with 2.3%having serious *** was a statistically significant difference in the number of enteroscopies between patients with and without canceration(P=0.004,Z=-2.882);71.2%of patients underwent surgical operation,75.6%of patients underwent surgical operation before the age of 35 years,and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer(P=0.000,Z=-5.127).At 40 years of age,the cumulative risk of intussusception in PJS was approximately 72.0%,and at 50 years,t

关键词： Peutz-Jeghers syndrome Management Intussusception Canceration stk11

Peutz-Jeghers综合征1例及其基因诊断

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第三军医大学学报 2011年第12期33卷 1249-1249,1257页

作者：于妍妍郭洪石彦刘丹许雪青白云第三军医大学基础部医学遗传学教研室第三军医大学西南医院全军普通外科中心微创胃肠外科中心第三军医大学学员旅17队

Peutz-Jeghers综合征（PJS）是一种常染色体显性遗传病,现行的临床诊断条件为消化道2个或2个以上经组织学证实的错构瘤性息肉、皮肤或黏膜色素沉着以及家族史[1]。研究[2]发现stk11基因是PJS的致病基因,主要参与调控细胞周期、代谢和极... 详细信息

Peutz-Jeghers综合征（PJS）是一种常染色体显性遗传病,现行的临床诊断条件为消化道2个或2个以上经组织学证实的错构瘤性息肉、皮肤或黏膜色素沉着以及家族史[1]。研究[2]发现stk11基因是PJS的致病基因,主要参与调控细胞周期、代谢和极性等。由于PJS患者的临床表现存在异质性,因此其确诊需借助于基因诊断。

关键词： Peutz-Jeghers综合征 stk11 基因诊断突变

Peutz-Jeghers综合征发病机制及临床诊治研究进展

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世界华人消化杂志 2019年第9期27卷 576-582页

作者：李白容孙涛蒋宇亮宁守斌中国人民解放军空军特色医学中心消化内科北京市100142

Peutz-Jeghers综合征(peutz-jeghers syndrome, PJS)是一种常染色体显性遗传疾病,目前已被证实的致病基因为stk11.该病的特征性表现为皮肤黏膜色素斑、消化道多发错构瘤性息肉及肿瘤易感性.基于目前研究报道, stk11胚系突变可能通过干... 详细信息

Peutz-Jeghers综合征(peutz-jeghers syndrome, PJS)是一种常染色体显性遗传疾病,目前已被证实的致病基因为stk11.该病的特征性表现为皮肤黏膜色素斑、消化道多发错构瘤性息肉及肿瘤易感性.基于目前研究报道, stk11胚系突变可能通过干扰正常的细胞凋亡、细胞分裂G1期阻滞、细胞极化及细胞间质水平的细胞增殖抑制等导致了PJS消化道息肉及恶性肿瘤的发生.治疗消化道息肉及息肉相关并发症是干预该病的主要手段.近年来,气囊辅助小肠镜治疗PJS小肠息肉经验不断积累、安全性得到了充分认可,使得大部分患者避免了外科开腹手术,这对改善了患者生活质量及远期预后有重要意义.另外,针对PJS随年龄增长消化道息肉生长特点及显著增加消化道及非消化道恶性肿瘤风险,我们按照年龄阶段进行有差别有针对的随访策略.

关键词： Peutz–Jeghers综合征 stk11 息肉恶性肿瘤气囊辅助小肠镜