CN111910006A - 前列腺癌及骨转移的诊疗靶点circ PLCL2 - Google Patents
前列腺癌及骨转移的诊疗靶点circ PLCL2 Download PDFInfo
- Publication number
- CN111910006A CN111910006A CN202010844598.8A CN202010844598A CN111910006A CN 111910006 A CN111910006 A CN 111910006A CN 202010844598 A CN202010844598 A CN 202010844598A CN 111910006 A CN111910006 A CN 111910006A
- Authority
- CN
- China
- Prior art keywords
- circ
- plcl2
- prostate cancer
- bone metastasis
- cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010060862 Prostate cancer Diseases 0.000 title claims abstract description 64
- 208000000236 Prostatic Neoplasms Diseases 0.000 title claims abstract description 64
- 101000691610 Homo sapiens Inactive phospholipase C-like protein 2 Proteins 0.000 title claims abstract description 47
- 102100026208 Inactive phospholipase C-like protein 2 Human genes 0.000 title claims abstract description 47
- 206010027476 Metastases Diseases 0.000 title claims abstract description 42
- 230000009401 metastasis Effects 0.000 title claims abstract description 42
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 40
- 238000003745 diagnosis Methods 0.000 title description 5
- 239000003147 molecular marker Substances 0.000 claims abstract description 12
- 230000009545 invasion Effects 0.000 claims abstract description 9
- 238000013508 migration Methods 0.000 claims abstract description 9
- 230000005012 migration Effects 0.000 claims abstract description 9
- 230000035755 proliferation Effects 0.000 claims abstract description 8
- 101000691618 Homo sapiens Inactive phospholipase C-like protein 1 Proteins 0.000 claims description 13
- 102100026207 Inactive phospholipase C-like protein 1 Human genes 0.000 claims description 13
- 229920000848 poly(L-lactide-ε-caprolactone) Polymers 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- 239000000523 sample Substances 0.000 claims description 10
- 206010027452 Metastases to bone Diseases 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 238000001514 detection method Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 101100520239 Homo sapiens PLCL2 gene Proteins 0.000 claims description 3
- 101150011211 PLCL2 gene Proteins 0.000 claims description 3
- 108020004459 Small interfering RNA Proteins 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 108091034117 Oligonucleotide Proteins 0.000 claims description 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 238000003209 gene knockout Methods 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 abstract description 18
- 230000003828 downregulation Effects 0.000 abstract description 4
- 239000003596 drug target Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 40
- 206010028980 Neoplasm Diseases 0.000 description 15
- 108091028075 Circular RNA Proteins 0.000 description 7
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000030279 gene silencing Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010041549 Spinal cord compression Diseases 0.000 description 1
- 208000005250 Spontaneous Fractures Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 101150018082 U6 gene Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000001617 migratory effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 210000000064 prostate epithelial cell Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明发现circ PLCL2在前列腺癌及其骨转移组织中高表达,并且下调circ PLCL2能够抑制前列腺癌增殖、迁移和侵袭,为此本发明提出circ PLCL2作为前列腺癌及其骨转移的分子标志物及药物靶点的用途。
Description
技术领域
本发明属于生物医学领域,更具体地,涉及前列腺癌及骨转移的诊疗靶点circPLCL2。
背景技术
前列腺癌(prostate cancer,PCa)是最易发生骨转移的肿瘤之一,占美国男性恶性肿瘤的第一位,死亡率仅次于肺癌。在我国,随着营养结构改变及老龄化趋势,PCa发病率和死亡率有显著增长的趋势。肿瘤发生骨转移后,伴随而来的是骨相关并发症,如疼痛、病理性骨折、高血钙症、脊髓压迫、运动功能丧失等,最终导致患者死亡。目前针对骨转移的治疗均属姑息性,无论是手术、放疗以及药物治疗,只是缓解及改善相应症状,并不能提高患者的生存预期。因而,一旦发生骨转移,不仅严重降低了患者的生活质量与寿命,也给临床治疗带来了极大的困难。与西方发达国家不同的是,我国前列腺癌发现时分期偏晚,肿瘤已经局部或远处转移,且低分化肿瘤占比高。目前尚无确切分子机制能够阐明前列腺癌转移,也没有相关靶标能够有效地预测前列腺癌转移。因此,寻找PCa骨转移的可能的靶点,从而为PCa患者骨转移提供新的特异性预测因子及治疗的潜在靶标,具有重要的现实意义和临床意义。
环状RNA(Circular RNA)于20世纪70年代在国外首先报道,环状RNA(circularRNA,circRNA)或称环形RNA,是新近确认的一类特殊的非编码RNA(non-coding RNA,ncRNA)分子,通常是通过特殊的选择性剪接机制而产生的包含一个以上外显子环化构成环状RNA,其几乎存在于所有物种,大量存在于真核细胞的细胞质中。circRNA在疾病中发挥着重要的调控作用,目前认识最多的是环状RNA通过结合miRNA来阻断后者对靶RNA的抑制作用,从而调控miRNA靶标的表达水平。目前研究已初步显示环状RNA在动脉粥样硬化、神经系统疾病、糖尿病及肿瘤的发生、发展中起着重要的作用。目前尚未有关于circ PLCL2与PCa骨转移关系的报道。
发明内容
本发明的目的在于提供前列腺癌及骨转移的诊疗靶点circ PLCL2。
本发明所采取的技术方案是:
检测分子标志物的试剂在制备前列腺癌的诊断工具中的用途,所述分子标志物为circ PLCL2。
优选的,其中试剂包括检测circ PLCL2的引物或探针。
检测分子标志物的试剂在制备前列腺癌骨转移的诊断工具中的用途,所述分子标志物为circ PLCL2。
优选的,其中试剂包括检测circ PLCL2的引物或探针。
下调circ PLCL2表达的制剂在制备预防或治疗前列腺癌的药剂中的用途。
优选的,其中制剂包括针对circ PLCL2的siRNA、反义寡核苷酸或敲除circ PLCL2基因的制剂。
优选的,其中药剂能够抑制前列腺癌骨转移细胞的增殖。
优选的,其中药剂能够抑制前列腺癌骨转移细胞的迁移。
优选的,其中药剂能够抑制前列腺癌骨转移细胞的侵袭。
本发明的有益效果是:
本发明发现circ PLCL2在前列腺癌及其骨转移组织中高表达,并且下调circPLCL2能够抑制前列腺癌增殖、迁移和侵袭,为此本发明提出circ PLCL2作为前列腺癌及其骨转移的分子标志物及药物靶点的用途。
附图说明
图1为组织及细胞系中circ PLCL2的表达情况;其中,图A为本发明所指circPLCL2的基本情况;图B为前列腺癌组织(Tumor)和良性前列腺组织(Bengin)中circ PLCL2表达情况;图C为配对癌旁正常组织(ANT)和肿瘤组织(Tumor)中circ PLCL2表达情况;图D为前列腺癌骨转移组织(PCa/BM)和无骨转移组织(PCa/nBM)中circ PLCL2分层表达情况,其中circ PLCL2-H为circ PLCL2高表达组,circ PLCL2-L为circ PLCL2低表达组;图E为前列腺癌骨转移组织(PCa/BM)和无骨转移组织(PCa/nBM)中circ PLCL2表达情况;图F为多种前列腺癌细胞中circ PLCL2表达情况;
图2为沉默circ PLCL2(si-circ PLCL2)和过表达circ PLCL2(circ PLCL2)的前列腺癌细胞的迁移和侵袭情况;
图3为沉默circ PLCL2(si-circ PLCL2)和过表达circ PLCL2(circ PLCL2)的前列腺癌细胞的增殖情况;
以上图中*和**均表示有显著统计学差异。
具体实施方式
下面结合具体实施例进一步阐述本发明,但并不局限于此。
下述实施例中所使用的实验方法或实验条件,如无特殊说明,均按常规方法或厂家说明书进行,下述实验中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
术语“非骨转移”或“无骨转移”在医学领域是指未发生伴骨转移,通常来说,对收集的肿瘤样本进行分析,如果肿瘤样本未发生骨转移,则归类为无骨转移肿瘤样本,本领域技术人员应该知晓,无骨转移肿瘤样本可能是未发生任何转移的肿瘤样本,也有可能是发生了其他非骨转移(如肝、脑、肺)的肿瘤样本。
实施例1、circ PLCL2在PCa组织及PCa骨转移组织中相对高表达
本实施例所用样本来自广州医科大学附属第二医院,样本包括良性前列腺组织26例和前列腺癌组织183例(其中,151例非骨转移前列腺癌组织和32例骨转移前列腺癌组织)。
本实施例所用细胞系包括人前列腺癌细胞系(22Rv1、PC-3、VCaP、DU145、LNCaP)和正常前列腺上皮细胞RWPE-1,均从中科院上海细胞库获得;人前列腺癌细胞C4-2B购自MD安德森癌症中心;其中,RWPE-1细胞用Defined Keratinocyte-SFM(1X)(Invitrogen公司)培养,PC-3、LNCaP、22Rv1细胞用含有青霉素G(100U/ml)、链霉素(100mg/ml)和10%胎牛血清(Life Technologies公司)的RPMI-1640培养基(Life Technologies公司)培养,DU145、VCaP细胞用含有10%胎牛血清的DMEM培养基(Invitrogen公司)培养;C4-2B细胞用含有10%胎牛血清的T培养基(Invitrogen公司)培养,以上细胞均在5%CO2,37℃条件下培养。
使用Trizol试剂提取RNA,将2μg RNA进行逆转录反应,反应完成后将cDNA保存于-20℃备用。按照检测试剂盒说明书准备DNA扩增所需要的SYBR Green mix(Roche),及相关引物。在Bio-rad实时定量PCR仪,根据试剂盒说明书要求设置扩增反应条件,进行40个循环反应。U6基因作为内参,所有样本至少设置3个副孔。目的基因DNA相对表达量通过Schmittgen and Livak2-ΔΔCt公式计算得出。检测circ PLCL2(分子详情参见图1A)和U6的引物由广州市锐博生物科技有限公司设计、合成和纯化。
结果如图1所示,与良性前列腺组织(Benign)相比,前列腺癌组织中circ PLCL2表达水平显著升高(图1B),10对配对的前列腺癌及癌旁组织中也是得出一致的结果(图1C);令人意外的是,在前列腺癌组织中,依据circ PLCL2表达水平中位值进行区分circ PLCL2高表达组(circ PLCL2-H)和circ PLCL2低表达组(circ PLCL2-L),结果发现,伴有骨转移的组织中circ PLCL2显著高表达(图1D和E),在前列腺癌细胞中也可以得出一致的结果(图1F)。
综上,circ PLCL2可作为前列腺癌诊断的分子标志物,以及前列腺癌骨转移的分子标志物,用于指导前列腺癌及骨转移的诊断试剂开发。
实施例2、circ PLCL2与PCa骨转移细胞体外侵袭、迁移相关
将人circ PLCL2基因克隆到pMSCV-puro逆转录病毒载体(Clontech公司)中,获得circ PLCL2表达质粒,分别将阴性对照质粒或circ PLCL2表达质粒转染到PC-3细胞、C4-2B细胞和VCap细胞中;将circ PLCL2 siRNA(简称si circ PLCL2)及阴性对照(NC)转染至PC-3细胞、C4-2B细胞和VCap细胞中,转染采用Lipofectamine 3000(Life Technologies公司)。
用50mg/L的matrigel包被或不包被transwell小室的polycarbonate滤膜,取含约5×104个PCa细胞的无血清培养基100μL加入transwell小室,下室加10%FBS的培养基作趋化剂。37℃培养24h,擦去膜上胶体,70%酒精固定膜上细胞,结晶紫染色。用100×显微镜进行观察和拍照,计数transwell底膜下侧附着的细胞。以穿膜细胞为侵袭细胞随机选择5个视野计数侵袭细胞,取平均值以侵袭细胞数来表示肿瘤细胞的侵袭或迁移能力。
结果如图2所示,circ PLCL2高表达促进PCa骨转移细胞体外侵袭、迁移,circPLCL2低表达抑制PCa骨转移细胞体外侵袭、迁移。
实施例3、沉默circ PLCL2抑制PCa骨转移细胞增殖
在构建的PC-3细胞、C4-2B细胞中进行细胞增殖检测,用0.25%胰蛋白酶消化细胞后,以细胞浓度3×104个/mL均匀接种于96孔培养板,每孔100μL,分别于0天,3天,5天通过加入MTT试剂10μL,37℃恒温箱孵育4h,每孔加入150ul二甲基亚砜,用多功能酶标仪检测各孔的吸光值A(490nm),以观察随着时间的变化,细胞增殖情况。
结果如图3所示,高表达circ PLCL2能够促进PCa骨转移细胞增殖,低表达circPLCL2能够抑制PCa骨转移细胞增殖。
综合实施例2和3的结果,可见下调circ PLCL2能够抑制前列腺癌细胞增殖、迁移和侵袭,能够发挥预防或治疗前列腺癌或其转移的作用,因此,下调circ PLCL2的制剂可以用于制备预防或治疗前列腺癌或其转移的药剂。
Claims (9)
1.检测分子标志物的试剂在制备前列腺癌的诊断工具中的用途,所述分子标志物为circ PLCL2。
2.根据权利要求1的用途,其中试剂包括检测circ PLCL2的引物或探针。
3.检测分子标志物的试剂在制备前列腺癌骨转移的诊断工具中的用途,所述分子标志物为circ PLCL2。
4.根据权利要求3的用途,其中试剂包括检测circ PLCL2的引物或探针。
5.下调circ PLCL2表达的制剂在制备预防或治疗前列腺癌骨转移的药剂中的用途。
6.根据权利要求5所述的用途,其中制剂包括针对circ PLCL2的siRNA、反义寡核苷酸或敲除circ PLCL2基因的制剂。
7.根据权利要求5所述的用途,其中药剂能够抑制前列腺癌骨转移细胞的增殖。
8.根据权利要求5所述的用途,其中药剂能够抑制前列腺癌骨转移细胞的迁移。
9.根据权利要求5所述的用途,其中药剂能够抑制前列腺癌骨转移细胞的侵袭。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010844598.8A CN111910006A (zh) | 2020-08-20 | 2020-08-20 | 前列腺癌及骨转移的诊疗靶点circ PLCL2 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010844598.8A CN111910006A (zh) | 2020-08-20 | 2020-08-20 | 前列腺癌及骨转移的诊疗靶点circ PLCL2 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111910006A true CN111910006A (zh) | 2020-11-10 |
Family
ID=73278488
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010844598.8A Pending CN111910006A (zh) | 2020-08-20 | 2020-08-20 | 前列腺癌及骨转移的诊疗靶点circ PLCL2 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111910006A (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080261908A1 (en) * | 2005-08-01 | 2008-10-23 | The Ohio State University | MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of breast cancer |
CN108624691A (zh) * | 2018-06-22 | 2018-10-09 | 杭州西合精准医疗科技有限公司 | 一种用于判断前列腺疾病的标志物及其应用 |
CN108624688A (zh) * | 2018-05-26 | 2018-10-09 | 复旦大学 | hsa_circ_0012755作为前列腺癌分子靶标在制备药物和试剂盒中的应用 |
CN108728535A (zh) * | 2018-05-26 | 2018-11-02 | 复旦大学 | hsa_circ_0049154作为前列腺癌分子靶标在制备药物和试剂盒中的应用 |
CN110643711A (zh) * | 2019-11-20 | 2020-01-03 | 广州医科大学附属第二医院 | 前列腺癌骨转移的生物标志物 |
-
2020
- 2020-08-20 CN CN202010844598.8A patent/CN111910006A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20080261908A1 (en) * | 2005-08-01 | 2008-10-23 | The Ohio State University | MicroRNA-based methods and compositions for the diagnosis, prognosis and treatment of breast cancer |
CN108624688A (zh) * | 2018-05-26 | 2018-10-09 | 复旦大学 | hsa_circ_0012755作为前列腺癌分子靶标在制备药物和试剂盒中的应用 |
CN108728535A (zh) * | 2018-05-26 | 2018-11-02 | 复旦大学 | hsa_circ_0049154作为前列腺癌分子靶标在制备药物和试剂盒中的应用 |
CN108624691A (zh) * | 2018-06-22 | 2018-10-09 | 杭州西合精准医疗科技有限公司 | 一种用于判断前列腺疾病的标志物及其应用 |
CN110643711A (zh) * | 2019-11-20 | 2020-01-03 | 广州医科大学附属第二医院 | 前列腺癌骨转移的生物标志物 |
Non-Patent Citations (3)
Title |
---|
姜涛等: "孤儿核受体在前列腺癌中的研究进展", 《实用肿瘤学杂志》 * |
陶伟: "睾丸孤核受体4(TR4)调控circPLCL2促进前列腺癌侵袭转移及其机制研究", 《中国优秀博硕士学位论文全文数据库(博士) 医药卫生科技辑》 * |
鲁菱娇等: "环状RNA(circRNA)在肿瘤中的研究进展", 《实验与检验医学》 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zhao et al. | RETRACTED: Circular RNA Cdr1as Upregulates SCAI to Suppress Cisplatin Resistance in Ovarian Cancer via miR-1270 Suppression | |
Huang et al. | The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro | |
Ge et al. | AntagomiR-27a targets FOXO3a in glioblastoma and suppresses U87 cell growth in vitro and in vivo | |
CN113462780B (zh) | 一种用于前列腺癌辅助诊断的标志物及试剂盒 | |
Zhai et al. | Analysis of clinical factors and PDGFR-β in predicting prognosis of patients with clival chordoma | |
He et al. | miR-452 promotes the development of gastric cancer via targeting EPB41L3 | |
CN111793694B (zh) | circ CDK13在前列腺癌骨转移中的用途 | |
CN112430665B (zh) | 一种诊治三阴性乳腺癌分子生物标志物及其应用 | |
Qian et al. | Downregulation of microRNA-144 inhibits proliferation and promotes the apoptosis of myelodysplastic syndrome cells through the activation of the AKAP12-dependent ERK1/2 signaling pathway | |
CN111910006A (zh) | 前列腺癌及骨转移的诊疗靶点circ PLCL2 | |
CN111893187B (zh) | circ AMOTL1在前列腺癌骨转移中的用途 | |
CN113293208B (zh) | 与肺癌增殖和转移相关的分子标志物及其应用 | |
WO2020073593A1 (zh) | 丝氨酸蛋白酶抑制因子Kazal 1型在制备细胞衰老及肿瘤诊断或调控制剂中的应用 | |
CN110819718A (zh) | miR-154-5p在前列腺癌骨转移的新应用 | |
CN113122638B (zh) | 一种hsa-novel_circ_0006787分子在肝癌治疗中的应用 | |
CN111808954B (zh) | lncRNA及其在疾病中的应用 | |
CN110628791A (zh) | 一种tRNA修饰酶基因在非小细胞肺癌中的应用 | |
CN114369667B (zh) | 长非编码rna在舌鳞癌诊治中的应用 | |
CN113122625B (zh) | Smco2基因作为标志物在子宫内膜癌中诊断及治疗的应用 | |
CN113122626B (zh) | Klc3基因作为标志物在卵巢癌中诊断及治疗的应用 | |
CN114042161B (zh) | Cenpw抑制剂在制备抗肿瘤药物中的应用 | |
CN109295015B (zh) | E3泛素连接酶trim7在肝癌中的应用 | |
KR102328654B1 (ko) | 암의 예방 또는 치료용 약학 조성물 | |
Tang et al. | miR-186 regulates epithelial-mesenchymal transformation to promote nasopharyngeal carcinoma metastasis by targeting ZEB1 | |
CN113528668A (zh) | 长链非编码rna-tuba4b的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201110 |