1.COPB1 promotes the development and progression of esophageal squamous cell carcinoma by activating the PI3K/AKT pathway and regulating the tumor immune microenvironment
LIN Yan ; YU Shuangjian ; JIA Sifan ; LI Feiyu ; ZHAO Chenpu ; DONG Zhiming ; SHEN Supeng ; LIANG Jia ; GUO Yanli
Chinese Journal of Cancer Biotherapy 2025;32(12):1236-1246
[摘 要] 目的:探究包被蛋白复合体β1亚基(COPB1)在食管鳞状细胞癌(ESCC)中的表达,及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法:采用2014~2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织,常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450,用转染试剂将pcDNA3.1-vector(空载体)、pcDNA3.1-COPB1载体,si-NC和si-COPB1转染至KYSE-150、TE1细胞中,记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系,qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况,WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达,克隆形成实验和MTS实验检测各组细胞的增殖能力,划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力,免疫组织化学染色(IHC)法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞(THP-1)构建巨噬细胞模型,用佛波酯(PMA)和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型,用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果:COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联(均P < 0.01),COPB1高表达的ESCC患者总生存期短(P < 0.05),COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达(均P < 0.05),过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力(均P < 0.05)。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路(均P < 0.001), COPB1可促进PI3K/AKT通路的活化(P < 0.05),COPB1高表达可导致M2型巨噬细胞浸润增加(P < 0.05),COPB1高表达促进TAM/M2极化(P < 0.05)。结论:COPB1在ESCC组织中呈高表达,其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展,COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。
2.Upregulation of LINC01503 expression by SOX9 promotes malignant biological behaviors and tumor stem cell stemness in laryngeal squamous cell carcinoma
WANG Jingtian a ; ZHAO Yan a ; LIU Shenghui a ; LAN Lili a ; WU Ganxun a ; SHEN Supeng b
Chinese Journal of Cancer Biotherapy 2024;31(11):1092-1100
[摘 要] 目的:探究SOX9通过上调长链非编码RNA LINC01503的表达对喉鳞状细胞癌(LSCC)细胞的增殖、迁移、侵袭及肿瘤干细胞干性的影响。方法: 常规培养人LSCC细胞AMC-HN-8、TU177、TU212和TU686,用转染试剂将敲减序列及其对照核酸(si-SOX9-NC、si-SOX9#1、 si-SOX9#2、si-LINC01503-NC、si-LINC01503#1、si-LINC01503#2)或过表达质粒及其对照核酸(pcDNA3.1-SOX-NC、pcDNA3.1-SOX-oe、pcDNA3.1-LIN01503-NC和pcDNA3.1-LIN01503-oe)分别转染至TU177细胞或TU686细胞,记为si-SOX9-NC组、si-SOX9#1组、si-SOX9#2组、si-LINC01503-NC组、si-LINC01503#1组、si-LINC01503#2组;pcDNA3.1-SOX9-NC组、pcDNA3.1-SOX9-oe组、pcDNA3.1-LINC01503-NC组、pcDNA3.1-LINC01503-oe组、si-SOX9-NC + pcDNA3.1-LINC01503-NC组和si-SOX9 + pcDNA3.1-LINC01503-oe组。qPCR法检测SOX9 mRNA和LINC01503 在各组细胞中的表达,生物信息学分析SOX9与LINC0503启动子区的结合位点,双萤光素酶报告基因实验和染色质免疫共沉淀实验验证SOX9与LINC01503启动子区是否直接结合,WB法检测SOX9的敲减效率及LINC01503对TU177和TU686细胞干性标志物表达的影响,MTS法检测各组细胞的增殖活力,划痕愈合和Transwell小室实验检测各组细胞的迁移能力,克隆形成实验检测各组细胞的克隆形成能力。结果:SOX9在各种LSCC细胞中呈高表达(均P < 0.05),数据库数据分析显示,在头颈部鳞状细胞癌中,SOX9与LINC01503表达呈正相关(R = 0.12,P = 0.005 9);SOX9可与LINC01503启动子区直接结合并促进其转录表达(均P < 0.05);敲减LINC01503可明显抑制TU177细胞的增殖、迁移、侵袭(均P < 0.05),过表达LINC01503明显促进TU686细胞增殖、迁移、侵袭的能力(均P < 0.05),提高TU686细胞克隆形成能力和细胞干性标志物分子CD133、OCT4、SOX2的mRNA和蛋白水平表达(均P < 0.05),敲减LINC01503则均可抑制TU686细胞的克隆形成和细胞干性标志物的表达(均P < 0.05);敲减SOX9均可明显抑制TU177细胞的增殖、迁移和侵袭能力,降低其干性细胞标志物的表达(均P < 0.05),同时过表达LINC01503则可部分逆转敲减SOX9对TU177细胞恶性生物学行为和干性标志物表达的抑制作用(均P < 0.05)。结论:SOX9和LINC01503在LSCC细胞中呈高表达,SOX9可能通过上调LINC01503表达提高LSCC细胞增殖、转移和侵袭能力和肿瘤干细胞干性。
3.Risk factors for pulmonary embolism in patients with acute spinal cord injury
Yijing LI ; Supeng YAN ; Yanxia SHAO ; Yuan YUAN ; Chunmei JIANG ; Shuyu PU ; Wei SUN
Journal of Army Medical University 2024;46(18):2130-2137
Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95%CI:1.532~2.499),length of ICU stay (P=0.000,OR=2.561,95%CI:1.728~3.794),number of operations (P=0.015,OR=1.814,95%CI:1.124~2.927),spinal fixation (P=0.004,OR=0.370,95%CI:0.189~0.724),restrictive position (P=0.000,OR=21.269,95%CI:5.276~85.740),platelet count (P=0.000,OR=1.553,95%CI:1.236~1.951),D-dimer level (P=0.000,OR=1.600,95%CI:1.376~1.860)and prothrombin time (P=0.025,OR=2.756,95%CI:1.138~6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.
4.Meta analysis of risk factors for pulmonary embolism in patients with spinal injury
Yijing LI ; Supeng YAN ; Xiaoping ZHOU ; Xiaoli WEN ; Tianjiao LI ; Xiangcheng HUANG ; Wei SUN
Chinese Journal of Trauma 2024;40(11):1000-1007
Objective:To evaluate the risk factors for pulmonary embolism in patients with spinal injury.Methods:Literature on risk factors for pulmonary embolism after spinal injury was searched on CNKI, Wanfang database, VIP Chinese Science, PubMed, Embase, Cochrane Library, Up to Date databases from inception through November 2023. A Meta-analysis was performed with the software of RevMan 5.4 after two researchers screened the literature independently according to the inclusion and exclusion criteria, extracted the data and evaluated their quality. Correlations of gender, age, surgical duration, intervertebral disc fusion, body mass index, comorbidity, medicine prophylaxis, deep venous thrombosis (DVT) history, and length of hospital stay with the incidence of pulmonary embolism in patients with spinal injury were evaluated.Results:A total of 10 studies were enrolled, including 2 prospective cohort studies and 8 cross-sectional studies. The total sample size was 401 698 patients, with 525 in the pulmonary embolism group and 401 173 in the non-pulmonary embolism group. The Meta analysis showed that gender ( OR=1.59, 95% CI 1.20, 1.97), age ( OR=1.58, 95% CI 1.19, 2.10), surgical duration ( OR=2.56, 95% CI 1.84, 3.56), DVT history ( OR=15.84, 95% CI 1.88, 133.25) and length of hospital stay ( OR=1.08, 95% CI 1.07, 1.09) were statistically significantly correlated with the incidence of pulmonary embolism in patients with spinal injury ( P<0.01), while intervertebral fusion, body mass index, comorbidity, and medicine prophylaxis were not correlated with the incidence of pulmonary embolism ( P>0.05). Conclusion:Gender, age, surgical duration, DVT history and length of hospital stay are risk factors for pulmonary embolism in patients with spinal injury.

Result Analysis
Print
Save
E-mail