目的 探讨LIM和SH3蛋白1(LIM and SH3 protein 1, LASP1)、激肽释放酶相关肽酶11(Kallikrein related peptidase 11, KLK11)表达水平与结直肠癌(Colorectal cancer, CRC)临床病理的关系及预后影响因素。方法 选择2017年1月至2018年10月...目的 探讨LIM和SH3蛋白1(LIM and SH3 protein 1, LASP1)、激肽释放酶相关肽酶11(Kallikrein related peptidase 11, KLK11)表达水平与结直肠癌(Colorectal cancer, CRC)临床病理的关系及预后影响因素。方法 选择2017年1月至2018年10月于本院就诊并接受手术治疗的82例CRC患者作为研究对象,术中收集癌组织和癌旁组织。免疫组织化学法检测癌旁组织和癌组织中LASP1和KLK11的阳性表达情况,分析LASP1和KLK11阳性表达与CRC临床病理的相关性。ROC曲线分析LASP1和KLK11在CRC诊断中的价值,分析LASP1和KLK11在CRC癌组织中表达的相关性。对患者进行5年随访并记录患者生存情况,确定LASP1和KLK11阳性表达与CRC患者生存的关系,Cox分析确定影响CRC患者生存的风险因素。结果 相对于癌旁组织,LASP1和KLK11在CRC癌组织中的阳性表达更高(P<0.05)。LASP1和KLK11表达与TNM分期和淋巴结转移有关(P均<0.05)。相对于Ⅰ/Ⅱ期和未发生淋巴结转移的患者,Ⅲ/Ⅳ期和发生淋巴结转移的患者中LASP1和KLK11表达为阳性的占比更高(P均<0.05)。ROC曲线分析结果显示,LASP1和KLK11能够作为CRC的有效诊断指标,且二者联合诊断价值更高。相关性分析结果显示,LASP1和KLK11在CRC癌组织中的表达呈正相关(r=0.33,P=0.003)。LASP1阳性和KLK11阳性患者的生存率显著低于LASP1阴性和KLK11阴性患者(P<0.05)。Cox多因素分析显示,分化程度、TNM分期、淋巴结转移、LASP1阳性表达、KLK11阳性表达是影响CRC患者预后的独立因素(P均<0.05)。结论 LASP1和KLK11阳性表达与CRC患者临床病理指标存在相关性,LASP1和KLK11表达或可作为CRC的有效诊断指标且与患者预后相关。展开更多
Background:Papillary thyroid cancer(PTC)is the most prevalent histological type of differentiated thyroid malignancy.Circular RNAs(circRNAs)have been implicated in the pathogenesis and progression of various cancers.c...Background:Papillary thyroid cancer(PTC)is the most prevalent histological type of differentiated thyroid malignancy.Circular RNAs(circRNAs)have been implicated in the pathogenesis and progression of various cancers.circTIAM1(hsa_circ_0061406)is a novel circRNA with aberrant expression in PTC.However,its functional roles in PTC progression remain to be investigated.Methods:The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR(qRT-PCR).The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization(FISH).Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression.Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs.RNA pulldown,RIP assay,and dual-luciferase reporter assay were used to confirm the interactions.Functional experiments,such as CCK-8,EDU staining,and apoptosis assays,as well as in vivo xenograft model were employed to explore the impacts of circTIAM1,miR-338-3p,and LIM/SH3 protein 1(LASP1)on the malignant phenotype of the PTC cells.Results:CircTIAM1 was highly expressed in PTC cells.Moreover,circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo.Furthermore,miR-338-3p was verified as a miRNA target of circTIAM1.LASP1 was also identified as a downstream target of miR-338-3p.The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays,which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.Conclusion:The overexpression of circTIAM1 is associated with the malignant progression of PTC.A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.展开更多
目的观察微小RNA(microRNA,miR)-6886-5p对LIM和SH3蛋白1(LIMandSH3 protein 1,LASP1)表达的调控作用及对胃癌细胞增殖和迁移的影响。方法2019年10月至2021年1月,使用实时定量聚合酶链式反应(qRT-PCR)检测胃癌细胞株和正常胃黏膜上皮细...目的观察微小RNA(microRNA,miR)-6886-5p对LIM和SH3蛋白1(LIMandSH3 protein 1,LASP1)表达的调控作用及对胃癌细胞增殖和迁移的影响。方法2019年10月至2021年1月,使用实时定量聚合酶链式反应(qRT-PCR)检测胃癌细胞株和正常胃黏膜上皮细胞中miR-6886-5p表达。以表达最低的细胞为实验对象,分为miR-6886-5p组(转染miR-6886-5p)和对照组(转染miR-NC)。使用淋巴细胞增殖检测(MTS)法和划痕愈合实验分别检测miR-6886-5p对胃癌细胞增殖和迁移能力的影响。使用生物信息学软件microRNA.org及双荧光素酶报告基因实验预测和验证miR-6886-5p的靶基因。使用qRT-PCR和Westernblot检测miR-6886-5p对靶基因表达的调控作用。结果与正常胃黏膜上皮细胞(GES-1)相比,胃癌细胞株miR-6886-5p表达明显下降(P<0.05),表达最低的细胞是HS-746T细胞(P<0.01)。对照组和miR-6886-5p组HS-746T细胞中miR-6886-5p表达分别为(1.17±0.40)和(9.48±1.10),差异有统计学意义(P<0.01)。与对照组相比,miR-6886-5p组细胞的增殖能力明显降低(P<0.05),迁移能力明显降低(P<0.01)。miR-6886-5p可能与LASP1基因的信使RNA(mRNA)存在结合位点。miR-6886-5p可靶向结合LASP1 mRNA(P<0.05)。与对照组相比,miR-6886-5p组LASP1基因表达明显下降(P<0.01)。结论miR-6886-5p在胃癌细胞株中呈低表达,miR-6886-5p能够通过调控LASP1基因表达,降低胃癌HS-746T细胞增殖和迁移能力。展开更多
目的分析LASP1(LIM and SH3 protein 1)和缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)在肺癌中的表达及其与临床因素之间的相关性。方法应用qRT-PCR、Western blot分别检测肺癌细胞株和正常肺细胞株间LASP1和HIF-1αmRNA...目的分析LASP1(LIM and SH3 protein 1)和缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)在肺癌中的表达及其与临床因素之间的相关性。方法应用qRT-PCR、Western blot分别检测肺癌细胞株和正常肺细胞株间LASP1和HIF-1αmRNA和蛋白表达差异,免疫组化分析肺癌患者LASP1和HIF-1α蛋白表达情况。结果 LASP1和HIF-1αmRNA和蛋白在肺细胞株中的表达明显低于在肺癌细胞株中的表达(P<0.05)。肺癌患者中LASP1表达与N分期(P=0.033)密切相关,HIF-1α与LASP1表达与T分期(P=0.027)和N分期(P=0.015)密切相关;LASP1和HIF-1α表达呈正相关(r=0.273,P=0.025)。预后生存分析发现N分期、LASP1和HIF-1α表达为本组肺癌患者预后独立因素。结论肺癌中LASP1和HIF-1α表达升高,LASP1和HIF-1α表达可作为肺癌预后预测指标。展开更多
目的:评价LASP1对口腔鳞癌细胞增殖、转移、侵袭和周期的影响,并对3种抗肿瘤药物顺铂、阿帕替尼和多西他赛的相关作用进行分析。方法:利用The human protein atlas数据分析LASP1与头颈部肿瘤生存率、预后的关系。RT-PCR和Western免疫印...目的:评价LASP1对口腔鳞癌细胞增殖、转移、侵袭和周期的影响,并对3种抗肿瘤药物顺铂、阿帕替尼和多西他赛的相关作用进行分析。方法:利用The human protein atlas数据分析LASP1与头颈部肿瘤生存率、预后的关系。RT-PCR和Western免疫印迹检测LASP1在口腔鳞癌细胞系的mRNA和蛋白表达。慢病毒构建LASP1沉默的HN30稳转细胞株,CCK-8法检测细胞增殖,平板克隆实验检测细胞克隆形成能力,Transwell法检测细胞转移和侵袭能力,流式细胞仪检测细胞周期变化。建立裸鼠口腔鳞癌肺部转移瘤。CCK-8法分析3种药物顺铂、阿帕替尼和多西他赛在细胞中的IC_50变化。采用SPSS 11.0软件包对数据进行统计学分析。结果:LASP1与头颈部肿瘤生存率、预后密切相关。LASP1促进口腔鳞癌细胞系HN30增殖、克隆形成、转移和侵袭,促进细胞周期G2/M期过渡。沉默LASP1后,裸鼠肺部转移瘤显著减少,多西他赛IC_50显著下调,而顺铂和阿帕替尼IC_50无显著变化。结论:LASP1促进口腔鳞癌细胞增殖、平板克隆、转移和侵袭,细胞周期G2/M期过渡,促进裸鼠体内肺转移瘤形成和多西他赛耐药。展开更多
基金the Ethics Committee of University-Town Hospital of Chongqing Medical University(LL-201682)the Laboratory Animal Ethics Committee of of University-Town Hospital of Chongqing Medical University(2022-053).
文摘Background:Papillary thyroid cancer(PTC)is the most prevalent histological type of differentiated thyroid malignancy.Circular RNAs(circRNAs)have been implicated in the pathogenesis and progression of various cancers.circTIAM1(hsa_circ_0061406)is a novel circRNA with aberrant expression in PTC.However,its functional roles in PTC progression remain to be investigated.Methods:The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR(qRT-PCR).The subcellular localization of circTIAM1 was examined by fluorescence in-situ hybridization(FISH).Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression.Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs.RNA pulldown,RIP assay,and dual-luciferase reporter assay were used to confirm the interactions.Functional experiments,such as CCK-8,EDU staining,and apoptosis assays,as well as in vivo xenograft model were employed to explore the impacts of circTIAM1,miR-338-3p,and LIM/SH3 protein 1(LASP1)on the malignant phenotype of the PTC cells.Results:CircTIAM1 was highly expressed in PTC cells.Moreover,circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo.Furthermore,miR-338-3p was verified as a miRNA target of circTIAM1.LASP1 was also identified as a downstream target of miR-338-3p.The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays,which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.Conclusion:The overexpression of circTIAM1 is associated with the malignant progression of PTC.A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.
文摘目的观察微小RNA(microRNA,miR)-6886-5p对LIM和SH3蛋白1(LIMandSH3 protein 1,LASP1)表达的调控作用及对胃癌细胞增殖和迁移的影响。方法2019年10月至2021年1月,使用实时定量聚合酶链式反应(qRT-PCR)检测胃癌细胞株和正常胃黏膜上皮细胞中miR-6886-5p表达。以表达最低的细胞为实验对象,分为miR-6886-5p组(转染miR-6886-5p)和对照组(转染miR-NC)。使用淋巴细胞增殖检测(MTS)法和划痕愈合实验分别检测miR-6886-5p对胃癌细胞增殖和迁移能力的影响。使用生物信息学软件microRNA.org及双荧光素酶报告基因实验预测和验证miR-6886-5p的靶基因。使用qRT-PCR和Westernblot检测miR-6886-5p对靶基因表达的调控作用。结果与正常胃黏膜上皮细胞(GES-1)相比,胃癌细胞株miR-6886-5p表达明显下降(P<0.05),表达最低的细胞是HS-746T细胞(P<0.01)。对照组和miR-6886-5p组HS-746T细胞中miR-6886-5p表达分别为(1.17±0.40)和(9.48±1.10),差异有统计学意义(P<0.01)。与对照组相比,miR-6886-5p组细胞的增殖能力明显降低(P<0.05),迁移能力明显降低(P<0.01)。miR-6886-5p可能与LASP1基因的信使RNA(mRNA)存在结合位点。miR-6886-5p可靶向结合LASP1 mRNA(P<0.05)。与对照组相比,miR-6886-5p组LASP1基因表达明显下降(P<0.01)。结论miR-6886-5p在胃癌细胞株中呈低表达,miR-6886-5p能够通过调控LASP1基因表达,降低胃癌HS-746T细胞增殖和迁移能力。
文摘目的分析LASP1(LIM and SH3 protein 1)和缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)在肺癌中的表达及其与临床因素之间的相关性。方法应用qRT-PCR、Western blot分别检测肺癌细胞株和正常肺细胞株间LASP1和HIF-1αmRNA和蛋白表达差异,免疫组化分析肺癌患者LASP1和HIF-1α蛋白表达情况。结果 LASP1和HIF-1αmRNA和蛋白在肺细胞株中的表达明显低于在肺癌细胞株中的表达(P<0.05)。肺癌患者中LASP1表达与N分期(P=0.033)密切相关,HIF-1α与LASP1表达与T分期(P=0.027)和N分期(P=0.015)密切相关;LASP1和HIF-1α表达呈正相关(r=0.273,P=0.025)。预后生存分析发现N分期、LASP1和HIF-1α表达为本组肺癌患者预后独立因素。结论肺癌中LASP1和HIF-1α表达升高,LASP1和HIF-1α表达可作为肺癌预后预测指标。
文摘目的:评价LASP1对口腔鳞癌细胞增殖、转移、侵袭和周期的影响,并对3种抗肿瘤药物顺铂、阿帕替尼和多西他赛的相关作用进行分析。方法:利用The human protein atlas数据分析LASP1与头颈部肿瘤生存率、预后的关系。RT-PCR和Western免疫印迹检测LASP1在口腔鳞癌细胞系的mRNA和蛋白表达。慢病毒构建LASP1沉默的HN30稳转细胞株,CCK-8法检测细胞增殖,平板克隆实验检测细胞克隆形成能力,Transwell法检测细胞转移和侵袭能力,流式细胞仪检测细胞周期变化。建立裸鼠口腔鳞癌肺部转移瘤。CCK-8法分析3种药物顺铂、阿帕替尼和多西他赛在细胞中的IC_50变化。采用SPSS 11.0软件包对数据进行统计学分析。结果:LASP1与头颈部肿瘤生存率、预后密切相关。LASP1促进口腔鳞癌细胞系HN30增殖、克隆形成、转移和侵袭,促进细胞周期G2/M期过渡。沉默LASP1后,裸鼠肺部转移瘤显著减少,多西他赛IC_50显著下调,而顺铂和阿帕替尼IC_50无显著变化。结论:LASP1促进口腔鳞癌细胞增殖、平板克隆、转移和侵袭,细胞周期G2/M期过渡,促进裸鼠体内肺转移瘤形成和多西他赛耐药。
