CN111748625B - miR-515-3p作为食管癌分子标志物的治疗应用 - Google Patents
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Abstract
本发明属于食管癌治疗领域,具体涉及miR‑515‑3p作为食管癌分子标志物的治疗应用。本发明首次发现了miR‑515‑3p及根据miR‑515‑3p序列合成的寡核苷酸能够有效抑制食管癌细胞的转移,且miR‑515‑3p可以作为食管癌治疗或预后标志物,对食管癌的治疗具有重要意义。
Description
技术领域
本发明属于食管癌治疗领域,具体涉及miR-515-3p作为食管癌分子标志物的治疗应用。
背景技术
食管癌是世界上一种常见的无法得到有效控制的高发消化道恶性肿瘤。五年生存率在15-25%之间。近年来对癌症的治疗方法有了很大的进步,但因其转移特性易复发,难以根治。上皮-间质转移(epithelial-to-mesenchymal transition,EMT)是一个表皮细胞获得间质特性的生物过程,是癌细胞转移的重要特征。多数癌症致死率高,预后差的重要原因是肿瘤细胞发生上皮-间质转化。EMT过程涉及众多蛋白,比如fibronectin,N-cadherin,E-cadherin等。而microRNA也被证明在细胞发生EMT过程中起着重要作用。
癌细胞转移是一个动态的连续的生物过程,包括从原发肿瘤分离、进入血管、形成转移灶等过程。有研究表明miRNAs和癌细胞转移有密切的关系,或可以作为治疗癌细胞转移的手段。miRNAs可通过和靶基因完全互补结合最后切割靶mRNA或者与靶基因不完全互补结合,进而阻遏翻译而不影响mRNA的稳定性。miRNA是基因表达和蛋白翻译过程中的调节分子,在肿瘤的发生发展过程中起到调控的枢纽作用。有10%-30%的人类基因转录组是miRNA的直接靶标。用它作为肿瘤的治疗手段或更加有效。然而,现有技术中尚未发现对有效治疗或抑制食管癌的MiRNA。
发明内容
为解决现有技术的缺点和不足之处,本发明的目的在于提供miR-515-3p作为食管癌治疗或预后标志物的应用,以及用于制备抑制食管癌细胞转移的药物的应用。本发明的目的还在于提供miR-515-3p寡核苷酸用于制备抑制食管癌细胞转移的药物的应用。
本发明的目的通过下述技术方案实现:
miR-515-3p在制备用于食管癌治疗或预后的试剂盒中的应用。
优选的,miR-515-3p在所述试剂盒中用作食管癌治疗或预后的标志物。
miR-515-3p用于制备治疗食管癌的药物的应用。
优选的,其中miR-515-3p用于抑制食管癌细胞的转移。
更优选的,其中miR-515-3p用于抑制食管癌细胞的侵袭。
优选的,其中miR-515-3p用于抑制EMT过程。
更优选的,其中miR-515-3p用于下调纤连蛋白和N-钙粘蛋白的表达和上调ZO-1和E-钙粘蛋白的表达。
miR-515-3p寡核苷酸用于制备治疗食管癌的药物的应用。
优选的,其中miR-515-3p寡核苷酸用于抑制食管癌细胞的转移。
更优选的,其中miR-515-3p寡核苷酸用于抑制食管癌细胞的迁移和侵袭。
本发明相对于现有技术具有如下的优点及效果:
本发明首次发现了miR-515-3p及根据miR-515-3p序列合成的寡核苷酸能够有效抑制食管癌细胞的转移,且miR-515-3p可以作为食管癌治疗或预后标志物,对食管癌的治疗具有重要意义。
附图说明
图1显示了实施例1中对正常食道组织和食道癌组织的染色分析,对应病人的生存分析,以及miR-515-3p在食管癌组织中的表达情况。
图2显示了实施例2中miR-515-3p对食管癌细胞迁移侵袭的影响。
图3显示了实施例3中miR-515-3p抑制裸鼠体内食管癌细胞转移的能力。
图4显示了实施例4中miR-515-3p寡核苷酸对食管癌细胞转移的抑制效果。
图5显示了实施例5中miR-515-3p寡核苷酸抑制裸鼠体内食管癌细胞转移的能力。
具体实施方式
下面结合实施例和附图对本发明作进一步详细的描述,但本发明的实施方式不限于此。
实施例1miR-515-3p在食管癌组织中的表达情况
基于70例正常的食道组织以及90例食道癌组织,分别进行染色分析,对应病人的生存分析以及检测miR-515-3p在食管癌组织中的表达情况,结果如图1所示。图1a中,miR-515-3p在45.7%(32/100)正常组织的表达量明显高于癌组织,而仅有22.0%(22/100)的癌组织有较高的miR-515-3p的表达。且将negative和weak分为低表达,moderate和strong分为高表达,据图1b显示miR-515-3p低表达预示着更差的生存率。此外,另筛选20例正常组织,8例原发瘤组织(T1&2),9例原发瘤组织(T3&4)和9例转移瘤组织研究miR-515-3p与肿瘤阶段的关系。图1c中显示miR-515-3p在正常组织中的表达量明显高于原发瘤(T1&2,T3&4)和转移瘤(metastatic tumors)。
实施例2miR-515-3p对食管癌细胞侵袭的抑制效果
通过裸鼠体内筛选得到高转移能力的细胞系KYSE150-Luc-LM3,并利用Transwell技术建立高侵袭能力的细胞系KYSE410-Luc-I6,具体方法参见Li,B.et al.Significanceof PI3K/AKT signaling pathway in metastasis of esophageal squamous cellcarcinoma and its potential as a target for anti-metastasistherapy.Oncotarget 8,38755-38766(2017)。随后,构建食管癌稳转过表达和敲低miR-515-3p和miR-CON(对照组)的上述两种细胞系,结果如图2a-c所示。图2a和2b中,过表达miR-515-3p显著抑制食管癌的侵袭。而且miR-515-3p可下调Fibronectin和N-cadherin的表达,上调ZO-1和E-cadherin的表达(图2c)。
另外基于类似的方法构建食管癌稳转过表达和敲低miR-515-3p和miR-CON的KYSE150-Luc和EC109细胞系,其中KYSE150-Luc的筛选参见Xu,W.W.et al.Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascularprogenitor cells to promote cancer progression.8,14399(2017),EC109可于上海中国科学院(Chinese Academy of Sciences,Shanghai)直接购买。图2d中显示已成功构建了敲低miR-515-3p的食管癌细胞系,侵袭实验显示敲低miR-515-3p可显著促进食管癌细胞的侵袭能力(图2e)并促进EMT过程(图2f)。
实施例3对miR-515-3p作用的体内实验
选取20只6周龄、雌性裸小鼠(balb/c-nu/nu),分为4组:过表达组(miR-515-3p,miR-CON)和敲低组(ZIP-miR-515-3p,ZIP-miR-CON),每组5只。
构建肿瘤转移模型:
(1)每只裸小鼠需打入106个食管癌细胞,细胞重悬于PBS中;
(2)用25G针头的微注射器取重悬细胞对裸鼠进行尾静脉注射。
(3)5至6周后,腹腔注射D-Luciferin(购自GOLDBIO),进行活体荧光拍照,观察癌细胞转移情况,结果如图3所示。图3a显示过表达miR-515-3p可抑制食管癌细胞的体内转移。图3b显示敲低miR-515-3p可促进食管癌细胞的体内转移,表明miR-515-3p可作为食管癌治疗和预后的标志物。
实施例4miR-515-3p寡核苷酸对食管癌细胞转移的抑制效果
利用食管癌细胞KYSE150-Luc-LM3转染miR-515-3p和miR-CON寡核苷酸,通过迁移侵袭实验检测miR-515-3p寡核苷酸对食管癌细胞迁移侵袭能力的影响,结果如图4所示。图4中结果表明过表达miR-515-3p寡核苷酸可以抑制食管癌细胞KYSE150-Luc-LM3的侵袭和迁移。
实施例5对miR-515-3p寡核苷酸作用的体内实验
选取10只6周龄、雌性裸小鼠(balb/c-nu/nu),对照组5只和实验组5只,构建肿瘤转移模型。
(1)每只裸小鼠需打入106个食管癌细胞KYSE150-Luc-LM3,细胞重悬于PBS中;
(2)用25G针头的微注射器取重悬细胞对裸鼠进行尾静脉注射。
(3)打入细胞大概二周后开始每周对实验组和对照组分别从尾静脉注射miR-515-3p和miR-CON寡核苷酸。
(3)9周后,腹腔注射D-Luciferin(购自GOLDBIO),进行活体荧光拍照,观察癌细胞转移情况,结果如图5所示。
图5显示miR-515-3p寡核苷酸体内结果。图5a中显示裸鼠体内miR-515-3p和miR-CON寡核苷酸转移的效果,右边的量化结果表明食管癌转移能力明显受到miR-515-3p寡核苷酸的抑制。图5b中HE染色结果同样显示515-3p寡核苷酸对食管癌细胞转移存在抑制作用。
上述实施例为本发明较佳的实施方式,但本发明的实施方式并不受上述实施例的限制,其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化,均应为等效的置换方式,都包含在本发明的保护范围之内。
Claims (4)
1.定量检测miR-515-3p的试剂在制备用于食管鳞癌预后诊断的试剂盒中的应用;其特征在于:所述的miR-515-3p的表达水平与患者总生存率呈正相关。
2.过表达miR-515-3p的试剂在制备用于治疗食管鳞癌的药物中的应用。
3.根据权利要求2所述的应用,其特征在于,其中过表达miR-515-3p的试剂用于抑制食管鳞癌细胞的转移。
4.根据权利要求2所述的应用,其特征在于,其中过表达miR-515-3p的试剂用于抑制食管鳞癌细胞的侵袭。
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Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103492590A (zh) * | 2011-02-22 | 2014-01-01 | 卡里斯生命科学卢森堡控股有限责任公司 | 循环生物标志物 |
CN104491877A (zh) * | 2014-12-11 | 2015-04-08 | 南通大学附属医院 | 一种miRNA在制备治疗食管癌的药物中的应用 |
CN104774929A (zh) * | 2015-03-18 | 2015-07-15 | 中山大学肿瘤防治中心 | miR-455-3p在食管鳞状细胞癌中的诊断、治疗和预后的应用 |
CN104873984A (zh) * | 2014-02-27 | 2015-09-02 | 中国医学科学院肿瘤医院 | microRNA-548k抑制剂在治疗和/或预防食管鳞状细胞癌中的用途 |
WO2015156964A1 (en) * | 2014-03-16 | 2015-10-15 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Microrna signature for predicting progression of barrett's esophagus |
CN108721316A (zh) * | 2018-05-15 | 2018-11-02 | 唐山市人民医院 | 标记物miR-652-5p对食管鳞癌转移、预后及治预在药物和试剂盒中的应用 |
CN110283912A (zh) * | 2019-07-18 | 2019-09-27 | 暨南大学 | has-miR-3656作为食管鳞癌分子标志物的应用 |
-
2020
- 2020-06-28 CN CN202010594259.9A patent/CN111748625B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103492590A (zh) * | 2011-02-22 | 2014-01-01 | 卡里斯生命科学卢森堡控股有限责任公司 | 循环生物标志物 |
CN104873984A (zh) * | 2014-02-27 | 2015-09-02 | 中国医学科学院肿瘤医院 | microRNA-548k抑制剂在治疗和/或预防食管鳞状细胞癌中的用途 |
WO2015156964A1 (en) * | 2014-03-16 | 2015-10-15 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Microrna signature for predicting progression of barrett's esophagus |
CN104491877A (zh) * | 2014-12-11 | 2015-04-08 | 南通大学附属医院 | 一种miRNA在制备治疗食管癌的药物中的应用 |
CN104774929A (zh) * | 2015-03-18 | 2015-07-15 | 中山大学肿瘤防治中心 | miR-455-3p在食管鳞状细胞癌中的诊断、治疗和预后的应用 |
CN108721316A (zh) * | 2018-05-15 | 2018-11-02 | 唐山市人民医院 | 标记物miR-652-5p对食管鳞癌转移、预后及治预在药物和试剂盒中的应用 |
CN110283912A (zh) * | 2019-07-18 | 2019-09-27 | 暨南大学 | has-miR-3656作为食管鳞癌分子标志物的应用 |
Non-Patent Citations (4)
Title |
---|
Donghu Yu et al.Comprehensive Analysis of Competitive Endogenous RNAs Network, Being Associated With Esophageal Squamous Cell Carcinoma and Its Emerging Role in Head and Neck Squamous Cell Carcinoma.《Frontiers in Oncology》.2020,第09卷 * |
Lina Mei et al.The prognostic and diagnostic values of MicroRNA-10b in gastric cancer:A comprehensive study based on meta-analysis and TCGA database.《Medicine》.2020,第99卷(第23期), * |
王锋 等.环状RNA在口腔鳞状细胞癌中的作用探讨.《中国口腔颌面外科杂志》.2019,第17卷(第06期), * |
胡学廷 等.环状RNA circPRDM5在食管鳞状细胞癌中的表达和功能研究.《岭南现代临床外科》.2019,第19卷(第02期), * |
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