搜索到164篇“ STK11“的相关文章
Two missense STK11 gene variations impaired LKB1/adenosine monophosphate-activated protein kinase signaling in Peutz-Jeghers syndrome
2024年
BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offspring from mutated genes;however,some variations in this gene have been interpreted as variants of uncertain significance(VUS),which complicate reproductive decision-making in genetic counseling.AIM To identify the pathogenicity of two missense variants and provide clinical guidance.METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya.Software was employed to predict the protein structure,conservation,and pathogenicity of the two missense variation sites in patients with PJS.Additionally,plasmids were constructed and transfected into HeLa cells to observe cell growth.The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry.Statistical analysis was performed using one-way analysis of variance.P<0.05 was considered statistically significant.RESULTS We identified two missense STK11 gene VUS[c.889A>G(p.Arg297Gly)and c.733C>T(p.Leu245Phe)]in 9 unrelated PJS families who were seeking reproductive assistance.The two missense VUS were located in the catalytic domain of serine/threonine kinase,which is a key structure of the liver kinase B1(LKB1)protein.In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK)at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells.In addition,the two missense STK11 variants promoted the proliferation of HeLa cells.Subsequent immunohistochemical analysis showed that phosphorylated-AMPK(Thr172)expression was significantly lower in gastric,colonic,and uterine polyps from PJS patients with missense variations than in non-PJS patients.Our fi
Jin LiuSi-Cong ZengAn WangHai-Ying ChengQian-Jun ZhangGuang-Xiu Lu
关键词:MISSENSESTK11
Corrigendum to ‘A novel STK11 gene mutation (c.388dupG,p.Glu130Glyfs∗33) in a Peutz-Jeghers family and evidence of higher gastric cancer susceptibility associated with alterations in STK11 region aa 107–170’ [Gene Dis (9) (2022) 288–291]
2024年
miR-627-3p并发靶向STK11/KEAP1调控肺腺癌的铁死亡研究被引量:1
2023年
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(P<0.05),铁死亡水平上升(P<0.05);敲低miR-627-3p后,肺腺癌细胞Calu-3的细胞增殖水平上升(P<0.05),铁死亡水平下降(P<0.05)。敲低STK11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平下降(P<0.05)、铁死亡水平上升(P<0.05);过表达STK11或KEAP1时肺腺癌细胞Calu-3的细胞增殖水平上升(P<0.05)、铁死亡水平下降(P<0.05)。过表达miR-627-3p后,肺腺癌细胞Calu-3中STK11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。
张苗苗田君娜孙颖颖
关键词:STK11KEAP1肺腺癌
Peutz-Jeghers syndrome without STK11 mutation may correlate with less severe clinical manifestations in Chinese patients被引量:1
2023年
BACKGROUND Peutz-Jeghers syndrome(PJS) is an autosomal dominant genetic disease with skin mucosal pigment spots and gastrointestinal(GI) multiple hamartoma polyps as clinical characteristics. At present, it is considered that the germline mutation of STK11 gene is the genetic cause of PJS. However, not all PJS patients can be detected STK11 germline mutations. The specific clinical characteristics of these PJS patients without STK11 mutation is an interesting clinical question. Or, like wild type GI stromal tumor, whether these PJS without STK11 mutation are also called PJS is worth discussing. Therefore, we designed the study to understand the clinical characteristics of these PJS patients without STK11 mutation.AIM To investigates whether PJS patients with known STK11 mutations have a more severe spectrum of clinical phenotypes compared to those without.METHODS A total of 92 patients with PJS admitted to the Air Force Medical Center from 2010 to 2022 were randomly selected for study. Genomic DNA samples were extracted from peripheral blood samples, and pathogenic germline mutations of STK11 were detected by high-throughput next-generation gene sequencing. Clinicalpathologic manifestations of patients with and without STK11/LKB1 mutations were compared.RESULTS STK11 germline mutations were observed in 73 patients with PJS. Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations. Compared with PJS patients with STK11 mutations, those without tended to be older at the age of initial treatment, age of first intussusception and age of initial surgery. They also had a lower number of total hospitalizations relating to intussusception or intestinal obstruction, and a lower load of small intestine polyps.CONCLUSION PJS patients without STK11 mutations might have less severe clinical-pathologic manifestations than those with.
Li-Xin JiangYu-Rui ChenZu-Xin XuYu-Hui ZhangZhi ZhangPeng-Fei YuZhi-Wei DongHai-Rui YangGuo-Li Gu
关键词:STK11
STK11基因突变的原发性腹膜上皮样间皮瘤1例
2023年
恶性腹膜间皮瘤(malignant peritoneal mesothelioma,MPM)是原发于腹膜的罕见恶性肿瘤。33%~50%的弥漫MPM患者有石棉接触史。发病年龄以50~70岁多见。近85%的MPM有BAP1基因改变。本文报道1例31岁女性上皮样型MPM无石棉接触史伴有遗传性肿瘤基因STK11突变。临床表现为盆腔肿块。镜下排列呈管状、条状、筛状,肿瘤细胞为上皮样,中度核异型性、有核仁,间质富含小血管,伴有广泛的黏液变性。免疫组织化学广谱细胞角蛋白、波形蛋白、Calretinin、D2-40、间皮素细胞、WT-1均阳性。全外显子基因检测示遗传性肿瘤基因STK11突变。腹腔镜手术并化疗后3个月盆腔肿物复发。
杜雪梅高颖苏延冬赵洪禹昌红李雁
关键词:间皮瘤盆腔肿物上皮样间皮素
二甲双胍克服STK11突变型肺癌免疫治疗耐药的效应和机制研究
研究背景及目的:  肺癌是我国发病率和死亡率最高的恶性肿瘤,非小细胞肺癌(Non-smallcelllungcancer,NSCLC)约占肺癌的85%,且大多数患者确诊时已为晚期,失去了根治性手术机会。免疫检查点抑制剂(...
王治国
关键词:肺癌二甲双胍
STK11<Sup>flox/flox</Sup>LTF<Sup>Cre/-</Sup>转基因小鼠子宫内膜肿瘤细胞系及其应用
本发明属于细胞系构建技术领域,尤其涉及一种STK11<Sup>flox/flox</Sup>LTF<Sup>Cre/‑</Sup>转基因小鼠子宫内膜肿瘤细胞系及其应用。所述STK11<Sup>flox/flox</Sup...
汪宏波章伟赵蓉张汤安苏张俊
广西壮族女性人群中ST K11基因遗传多态性的研究
2022年
目的探讨广西壮族正常女性人群STK11基因rs12977689、rs60755851和rs9282860的基因多态性,并分析其与不同国家或地区正常女性人群的分布差异。方法采用荧光多重酶连接反应(imLDR)技术检测2018—2020年在广西右江民族医学院附属医院体检的351例广西壮族正常女性人群STK11基因多态性位点rs12977689、rs60755851和rs9282860的基因型,采用Sanger测序法作为验证,并与千人基因组计划数据库中的非洲、美国、日本、欧洲、南亚、印度和北京汉族等地区的正常女性人群进行比较。结果rs12977689有CC、CA、AA三种基因型,频率分别为51.0%、44.2%、6.8%;rs60755851有AA、CA、CC三种基因型,频率分别为37.3%、50.2%、12.4%;rs9282860有CC、CT、TT三种基因型,频率分别为70.9%、27.4%、1.7%。广西壮族正常女性人群的rs12977689和rs60755851基因型和等位基因频率与非洲、美国、欧洲、南亚和印度的正常女性人群的分布比较差异均具有统计学意义(P<0.05),rs9282860的基因型和等位频率与非洲、欧洲和日本地区的正常女性人群的分布比较差异均具有统计学意义(P<0.05)。结论STK11基因rs12977689、rs60755851和rs9282860在广西壮族正常女性人群中存在遗传多态性,其与不同国家或地区正常女性人群的遗传多态性差异可作为后续研究不同人群疾病易感性的理论依据。
凌永嫦仇雯丽王俊利吴惠珍
关键词:STK11遗传多态性
STK11基因突变与非小细胞肺癌免疫治疗相关性研究进展被引量:1
2022年
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。
夏思雨赵梓彤李里
关键词:STK11基因突变免疫治疗
A novel STK11 gene mutation (c.388dupG,p.Glu130Glyfs∗33) in a Peutz-Jeghers family and evidence of higher gastric cancer susceptibility associated with alterations in STK11 region aa 107-170被引量:1
2022年
Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and gastrointestinal(GI)hamartomatous polyposis and is associated with an increased risk of gastrointestinal,breast,gynecologic and other extra-GI malignancies.The serine/threonine kinase 11(STK11)gene has been identi-fied as a pathogenic factor in PJS.STK11 is a tumor sup-pressor gene located on chromosome 19p13.3 and includes 9 coding exons.1 The STK11 protein is composed of 433 amino acids(aa)and comprises a kinase catalytic region(aa 49e309)as well as N-and C-terminal regulatory domains.
Giovanna ForteFilomena CariolaKatia De MarcoAndrea ManghisiFilomena Anna GuglielmiRaffaele ArmentanoGiuseppe LippolisPietro GiorgioCristiano SimoneVittoria Disciglio
关键词:STK11

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施小六
作品数:51被引量:180H指数:7
供职机构:中南大学湘雅二医院
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宁文锋
作品数:6被引量:22H指数:3
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