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 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
目的探究微小RNA-625-5p(miR-625-5p)是否可靶向LIM和SH3结构域蛋白1(LIM and SH3 protein 1,LASP1)影响结直肠癌(colorectal cancer,CRC)细胞的增殖、迁移及凋亡。方法CRC细胞转染后分为空白对照组、阴性对照组、miR-625-5p类似物组、m...目的探究微小RNA-625-5p(miR-625-5p)是否可靶向LIM和SH3结构域蛋白1(LIM and SH3 protein 1,LASP1)影响结直肠癌(colorectal cancer,CRC)细胞的增殖、迁移及凋亡。方法CRC细胞转染后分为空白对照组、阴性对照组、miR-625-5p类似物组、miR-625-5p抑制剂组、miR-625-5p类似物+LASP1组。进行荧光定量聚合酶链式反应(quantitative polymerase chain reaction,qPCR)检测各组LASP1、miR-625-5p的mRNA表达,双荧光素酶报告基因检测基因靶向结合关系,细胞计数试剂盒(cell counting kit,CCK)-8检测细胞活性,细胞平板克隆检测细胞克隆能力,流式细胞术检测细胞凋亡,Transwell法检测细胞迁移及侵袭,EDU实验测定细胞增殖,蛋白免疫印迹(Western blot)法检测LASP1及侵袭转移相关蛋白神经型钙黏蛋白(neural cadherin,N-cadherin)和上皮型钙黏蛋白(epithelial cadherin,E-cadherin)的表达情况。结果qPCR检测证明细胞转染成功,双荧光素酶报告基因检测到miR-625-5p可靶向结合LASP1。与阴性对照组比较,miR-625-5p类似物组的细胞活性和细胞克隆、迁移、侵袭、增殖数量及LASP1、N-cadherin表达水平降低(P<0.05),细胞凋亡率及E-cadherin表达水平上升(P<0.05),miR-625-5p抑制组上述指标的结果完全相反。与miR-625-5p类似物组比较,miR-625-5p类似物+LASP1组的细胞活性和细胞克隆、迁移、侵袭、增殖数量及LASP1蛋白表达水平升高(P<0.05),细胞凋亡率降低(P<0.01)。结论miR-625-5p可靶向LASP1抑制结直肠癌细胞的增殖、迁移,并促进凋亡。展开更多
目的探究LASP1蛋白(LIM and SH3 protein 1)在胶质母细胞瘤组织中的表达及其与患者临床病理特征、耐药和预后的关系。方法采用免疫组织化学法检测LASP1在140例胶质母细胞瘤组织和15例正常脑组织中的表达,分析其表达及与患者临床和预后...目的探究LASP1蛋白(LIM and SH3 protein 1)在胶质母细胞瘤组织中的表达及其与患者临床病理特征、耐药和预后的关系。方法采用免疫组织化学法检测LASP1在140例胶质母细胞瘤组织和15例正常脑组织中的表达,分析其表达及与患者临床和预后的关系。结果与正常脑组织相比,LASP1在胶质母细胞瘤组织中表达明显升高(P <0.01),并且与肿瘤Ki67的表达、肿瘤大小、囊性改变相关(均P <0.05)。Kaplan-Meier生存分析显示,LASP1高表达患者中位生存时间、无复发中位生存时间较低表达患者均明显缩短(均P <0.01);替莫唑胺化疗在高表达患者中无明显生存获益(P> 0.05)。单因素及Cox多因素分析提示,LASP1的表达及替莫唑胺化疗是胶质母细胞瘤独立危险因素(均P <0.05)。结论 LASP1在胶质母细胞瘤中高表达,与患者预后及替莫唑胺敏感性相关,其可能是胶质母细胞瘤潜在的治疗靶点和预后评估的分子标志物。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.
