CN117603966A - 一种具有抑制肺腺癌细胞增殖功能的circRNA及其应用 - Google Patents
一种具有抑制肺腺癌细胞增殖功能的circRNA及其应用 Download PDFInfo
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- 208000010507 Adenocarcinoma of Lung Diseases 0.000 title claims abstract description 34
- 201000005249 lung adenocarcinoma Diseases 0.000 title claims abstract description 34
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- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 101150053469 SDHC gene Proteins 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
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- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 108091028075 Circular RNA Proteins 0.000 description 1
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- C—CHEMISTRY; METALLURGY
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/532—Closed or circular
Abstract
本发明涉及生物技术领域，具体涉及一种具有抑制肺腺癌细胞增殖功能的circRNA及其应用；本发明首次公开了circSDHC用于肺腺癌细胞的增殖速率具有明显的抑制的用途，该抑制作用申请人通过实验进行验证获得肯定，而基于公开的特点有望基于此开发有关肺腺癌相关用途。
Description
技术领域
本发明涉及生物技术领域，具体涉及一种具有抑制肺腺癌细胞增殖功能的circRNA及其应用。
背景技术
肺癌是全球死亡率第一、发病率第二的恶性肿瘤。在中国，肺癌同样是危害人群健康的首要恶性肿瘤。其中肺腺癌(Lung adenocarcinoma,LUAD)是非小细胞肺癌(Non-smallcell lung carcinoma,NSCLC)的主要病理类型，肺腺癌的治疗取得重要突破，已由传统的手术治疗、化疗和放疗，发展到精准分子靶向治疗和免疫治疗，但大部分患者治疗后最终都会产生耐药，其肺腺癌患者的5年生存率低于16.1％，疗效仍不令人满意[2,3]。因此，深入探索肺腺癌发病的分子机制，寻找新的防治靶点和药物，具有非常重要的科学意义和临床实用价值。
circRNA由于其特殊的环状结构，序列高度保守，并且结构更加稳定，因此越来越多的研究认为，circRNA的这种特殊的结构性质，可以使它成为多种疾病的理想的生物标志，以及药物治疗研究的新靶点。越来越多的研究表明，circRNA参与了包括肺腺癌在内的肿瘤发生和发展过程，并且可以作为新型的肿瘤生物标志物和精准治疗靶点，在临床诊断和治疗领域具有广阔的应用前景。
发明内容
本发明的目的在于提供一类用作肺腺癌细胞增值抑制的circRNA，该circRNA在肺腺癌组织和癌旁组织标本中存在差异表达。
本发明通过TCGA数据库分析circRNA在肺腺癌组织和癌旁组织标本的表达谱，发现多个circRNA表达水平显著改变，其中circRNA0015004，circRNA0000515，circRNA0000520表达上调最为显著。
基于以上线索，申请人通过RT-qPCR进一步验证circRNA在肺腺癌组织和癌旁组织标本中的差异表达，结果显示，circRNA0015004在肺腺癌组织中表达明显升高，且circRNA0015004高表达的肺腺癌患者总体生存期更短，差异具有统计学意义(P＝0.0019)；
circRNA0015004是起源于1号染色体长臂上的SDHC基因，全长为385nt，由外显子2,3,4和5反向剪接而形成的外显子环状RNA，所以命名为“circSDHC”。
本发明的circSDHC的序列如下SEQ ID NO.1：
AACGTGTCAAGTGTCGGAT
借由上述方案及说明，本发明至少具有以下优点：
本发明的优点在于首次公开了circSDHC用于肺腺癌细胞的增殖速率具有明显的抑制的用途，该抑制作用申请人通过实验进行验证获得肯定，而基于公开的特点有望基于此开发有关肺腺癌相关用途。
附图说明
为了使本发明的内容更容易被清楚的理解，下面根据本发明的具体实施例并结合附图，对本发明作进一步详细的说明。
图1示本发明circSDHC在肺腺癌中高表达图。
图2示本发明circSDHC的高表达与肺腺癌患者不良预后示意图。
图3示本发明circSDHC成环的结构示意图(exon指外显子)。
图4示本发明circSDHC对肺腺癌细胞增殖的影响。
具体实施方式
下面结合附图和具体实施例对本发明作进一步说明，需要说明的是，在相互不冲突的情况下，本申请的实施例及实施例中的特征可以相互组合。
结合图1-4所示的，本发明申请人通过TCGA数据库分析circRNA在肺腺癌组织和癌旁组织标本的表达谱，发现多个circRNA表达水平显著改变，其中circRNA0015004，circRNA0000515，circRNA0000520表达上调最为显著(图1A-B)；
进而申请人通过RT-qPCR进一步验证circRNA在肺腺癌组织和癌旁组织标本中的差异表达，结果显示circRNA-0015004在肺腺癌组织中表达明显升高(图2-A)，且circRNA0015004高表达的肺腺癌患者总体生存期更短，差异具有统计学意义(P＝0.0019)(图2-B)。
基于上述结论，确定的circRNA0015004是起源于1号染色体长臂上的SDHC基因，全长为385nt，由外显子2,3,4和5反向剪接而形成的外显子环状RNA(图3)，所以命名为“circSDHC”，本发明的circSDHC的核苷酸序列如下SEQ ID NO.1：AACGTGTCAAGTGTCGGAT
验证：
本发明申请人选取H1299和A549细胞转染circSDHC的shRNA序列(si-circSDHC)，shRNA(si-NC)序列作为阴性对照组。
通过克隆形成实验检测circSDHC阴性对照组(si-NC)和circSDHC敲减组(si-circSDHC#1)细胞的增殖能力。
结果提示，敲减circSDHC抑制了H1299和A549人肺腺癌细胞克隆形成。EDU实验结果显示，与sh-NC对照组相比，circSDHC敲减组(si-circSDHC#1)红色荧光减少，结果表明敲减circSDHC可显著降低肺腺癌细胞的增殖速率(图4A-B)。
基于上述的实验结果结论，申请人表示，circSDHC完全满足对肺腺癌细胞的具有明显的增殖速率抑制作用，该抑制作用申请人通过实验进行验证获得肯定，即有望基于此开发包括不限于有关肺腺癌相关的抑制药物以及治疗方向上的研究药物用途。
显然，本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。
Claims (3)
1.一种具有抑制肺腺癌细胞增殖功能的circRNA，其特征在于：所述circRNA命名为circSDHC，其核苷酸序列为SEQ ID NO.1。
2.一种如权利要求1所述的circSDHC在制备抑制肺腺癌细胞的产品中的应用。
3.一种如权利要求1所述的circSDHC在制备治疗肺腺癌的药物中的应用。
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