CN109355391A - Application of the LINC01876 as the molecular marker of diagnosing liver cancer - Google Patents
Application of the LINC01876 as the molecular marker of diagnosing liver cancer Download PDFInfo
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- CN109355391A CN109355391A CN201811481731.7A CN201811481731A CN109355391A CN 109355391 A CN109355391 A CN 109355391A CN 201811481731 A CN201811481731 A CN 201811481731A CN 109355391 A CN109355391 A CN 109355391A
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Abstract
The present invention provides purposes of the LINC01876 as the molecular marker of diagnosing liver cancer.It is of the invention research shows that expression of the LINC01876 in liver cancer tissue and in cancer beside organism there are significant differences, think that LINC01876 can be used as the molecular marker of diagnosing liver cancer accordingly.The product that can be used for early diagnosing liver cancer is developed according to the studies above achievement, the product recall rate is good, is suitble in clinical expansion.
Description
Technical field
The invention belongs to fields of biomedicine, are related to application of the LINC01876 as the molecular marker of diagnosing liver cancer.
Background technique
Primary carcinoma of liver (primary carcinoma of liver, hereinafter referred to as liver cancer) is common pernicious swollen in China
One of tumor.It is counted according to the 1990s, the annual death rate of China's liver cancer is 20.37/10 ten thousand, in mortality of malignant tumors cis-position
The 2nd is accounted for, lung cancer is only second in city；Gastric cancer is only second in rural area.Due to serum alpha-fetoprotein (AFP) clinical application and
The progress of various Imaging Technologies, especially AFP and ultrasonoscopy are used for the monitoring of liver cancer high risk population, enable liver cancer in nothing
The Patients with Subclinical of sings and symptoms makes diagnosis, in addition the No operations such as the maturation of surgery operating technology and various local treatments
The development for the treatment of method makes the prognosis of liver cancer be significantly improved more in the past.
The clinical manifestations pole of primary carcinoma of liver is not true to type, and how unobvious symptom is generally, especially in course of disease early stage.Usually
5cm or less small liver cancer about 70% or so is asymptomatic, asymptomatic subclinical carcinoma of liver also 70% or so be small liver cancer.Symptom once goes out
It is existing, illustrate that tumour is larger, then generally mostly rapidly, cachexia is presented, often in the progress of patient's condition usually within several weeks
It is that failure is dead within some months to 1 year.Clinical manifestations be mainly two aspect lesion: the 1. performance of cirrhosis, as ascites,
The oedema etc. of the generation of Doppler flow mapping, spitting blood and limbs；2. symptom caused by tumour itself, such as weight loss, the whole body it is out of strength,
Hepatalgia and liver enlargement etc..
In any area in the world all also, it was found that chronic liver disease caused by any reason all may be in liver cancer occurrence and development
It plays an important role in the process.Epidemiology and experimental study show that virus hepatitis and primary carcinoma of liver have
Specific relationship relatively explicitly has B-mode, the third type and 3 kinds of fourth type with the related virus hepatitis of liver cancer at present.Wherein with
Hepatitis B is the closest with Relations with Liver Cancer, in recent years HBsAg negative HCC number increase it is related with hepatitis C, and the former Soviet Union then with
Fourth type is more.About 90% has hepatitis type B virus (HBV) to infect background in China's liver cancer patient.Other risk factors include alcohol
Property cirrhosis, adenoma of liver, for a long time take in aflatoxins, other kinds of chronic active hepatitis, Wilson disease, tyrosinemia
And glycogenic thesaurismosis.
The currently used method for diagnosing cancer of liver includes such as under type:
1, laboratory checks
(1) blood serum designated object of the detection of liver cancer marker in recent years for liver cancer detection mainly has: 1. alpha-fetoprotein
(AFP) and its heteroplasmon；2. various sero-enzymes, such as γ glutamyl transpeptidase isodynamic enzyme II test (GGT- II), the same work of alkaline phosphatase
Enzyme I (ALP- I), aldolase isodynamic enzyme A (ALD-A), fucosidase (AFU), antitrypsin I (AAT), 5 ' nucleotide phosphodiesterases
Diester enzyme isoenzyme V (5 '-NPD-V), pyruvate kinase isodynamic enzyme (M2-PyK), glutathione S-transferase (GST) etc.；3. different
Normal factor；4. ferritin and Acidic Ferritin.Wherein the diagnostic value of AFP is maximum.Diagnosis for AFP negative liver cancer,
Above several blood serum designated object use in conjunction, have certain diagnostic value.
2, other auxiliary examinations
(1) ultrasonic examination；(2) computer x-ray body layer scanning (CT)；(3) Magnetic Resonance Imaging (MRI)；(4) arteria hepatica is made
Shadow；(5) radionuclide image；(6) liver puncture biopsy.
But using the defect of blood serum designated object diagnosing liver cancer be it is insensitive, utilize lacking for other auxiliary examination diagnosing liver cancers
Falling into is that cannot make diagnosis in disease early stage, delays the state of an illness.It is falling ill early stage i.e. to improve the cure rate key of liver cancer
Accurate diagnosis can be made, the purpose of the application research is to find the early stage that can be used in diagnosing cancer of liver at the genetic level thus
Molecular marker.
Summary of the invention
For overcome the deficiencies in the prior art, the purpose of the present invention is to provide a kind of non-volumes of the long-chain for diagnosing liver cancer
Code RNA marker.The present invention is using chip and QPCR experiments have shown that expression of the LINC01876 in liver cancer tissue is obviously high
In the level in cancer beside organism, therefore can be using LINC01876 as the molecular marker of diagnosing liver cancer.
In order to test above-mentioned purpose, present invention employs following technical solutions:
The present invention provides the reagents of detection long-chain non-coding RNA expression to produce in preparation diagnosis for liver cancer or prognosis prediction
Application in product；The encoding gene Gene ID:101929378 of the long-chain non-coding RNA.
Long-chain non-coding RNA of the invention is named as LINC01876 in NCBI.Belong to gene I/D: 101929378 compile
The LINC01876 transcript of code product includes: NR_110249.2 (1773bp, corresponding DNA sequence dna are SEQ ID NO.1)；
NR_110250.2 (1823bp, corresponding DNA sequence dna are SEQ ID NO.2).
Further, the reagent including the use of SYBR Green, TaqMan probe, molecular beacon, double cross probe or is answered
The PCR amplification primer used when closing probe in detecting LINC01876 expression quantity.
In specific embodiments of the present invention, the primer sequence is as shown in SEQ ID NO.3 and SEQ ID NO.4.
The present invention provides a kind of for diagnosis for liver cancer or the product of prognosis prediction, the product include detection
The reagent of LINC01876 expression.
Further, the reagent includes SYBR Green, TaqMan probe, molecular beacon, double cross probe or compound spy
Needle detects the PCR amplification primer used when LINC01876 expression quantity.
In specific embodiments of the present invention, the primer sequence is as shown in SEQ ID NO.3 and SEQ ID NO.4.
Further, mentioned-above product includes but is not limited to chip, kit, test paper or high-flux sequence platform；It is high
Flux microarray dataset is a kind of tool of special diagnosing liver cancer, with the development of high throughput sequencing technologies, to the RNA of a people
The building of express spectra will become very easily work.By the rna expression of comparison Disease and normal population spectrum, it is easy to divide
The exception which RNA is precipitated is related to disease.Therefore, LINC01876 abnormal expression and liver cancer phase are known in high-flux sequence
The purposes for also belonging to LINC01876 is closed, equally within protection scope of the present invention.
The kit include detect LINC01876 expression quantity reagent, the reagent include with LINC01876 or its
The nucleic acid that DNA sequence dna combines, the nucleic acid include SYBR Green, TaqMan probe, molecular beacon, double cross probe or multiple
The PCR amplification primer used when closing probe in detecting LINC01876 expression quantity.
The chip includes the reagent for detecting LINC01876 expression quantity, and the reagent includes and LINC01876 or its DNA
The nucleic acid that sequence combines, the nucleic acid includes the probe for being able to detect LINC01876 expression quantity.
The test paper includes the reagent for detecting LINC01876 expression quantity, and the reagent includes and LINC01876 or its DNA
The nucleic acid that sequence combines, the nucleic acid includes the probe for being able to detect LINC01876 expression quantity.
The present invention provides a kind of for treating the pharmaceutical composition of liver cancer, and described pharmaceutical composition includes LINC01876
Inhibitor.
Further, the inhibitor is unrestricted, as long as can inhibit LINC01876 expression or inhibition
LINC01876 functional activity.
The inhibitor includes siRNA, shRNA, suppressive miRNA or suppressive targeting small molecule compound.
Pharmaceutical composition of the invention can be used as medicine and be administered alone or apply together with other medicines.It can be with this hair
The other medicines that bright pharmaceutical composition is applied together are unrestricted, as long as it does not damage therapeutic or preventative medicine of the invention
The effect of compositions, it is preferred that the drug for treating or preventing tumour may include such as alkylating agent, such as different
Cyclophosphamide, cyclophosphamide, Dacarbazine, Temozolomide, Nimustine, busulfan, procarbazine, melphalan and Lei Mosi
Spit of fland；Antimetabolite, such as enocitabine, capecitabine, Carmofur, Cladribine, gemcitabine, cytarabine, cytarabine
Octadecyl phosphate (cytarabine ocfosfate), Tegafur, tegafur-Uracil, Tegafur gimeracil Austria replace
Draw western potassium, doxifluridine, hydroxycarbamide, fluorouracil, fludarabine, pemetrexed, Pentostatin, mercaptopurine and first ammonia butterfly
Purine；Plant alkaloid, such as Irinotecan, Etoposide, Sobuzoxane, docetaxel, nogitecan, Palmer altruism, Changchun
Rui Bin, eldisine and vincaleukoblastinum；Antitumor antibiotic, such as actinomycin D, Aclarubicin, Amrubicin, idarubicin, table
It is soft more mould than star, Zinostatin stimalamer, daunorubicin, Doxorubicin, pirarubicin, bleomycin, Peplomycin, mitogen
Plain C and mitoxantrone；Drug based on platinum, such as oxaliplatin, carboplatin, cis-platinum and Nedaplatin；Hormonal medicaments, such as Ah that
Bent azoles, Exemestane, Estramustine, ethinyloestradiol, chlormadinone, Goserelin, tamoxifen, dexamethasone, Toremifene, ratio
Card Shandong amine, Flutamide, prednisolone, Fosfestrol, mitotane, methyltestosterone, Medroxyprogesterone, Mepitiostane, Leuprorelin and come it is bent
Azoles；Biological response modifier, such as interferon-' alpha ', interferon beta, interferon gamma, interleukin, ubenimex, dry BCG and mushroom are more
Sugar；And molecular targeted agents, such as Imatinib (imatinib), Gefitinib (gefitinib), gemtuzumab, Ao Zuo meter
Star, Tamibarotene, trastuzumab, Tretinoin, bortezomib (bortezomib) and Rituximab etc..
Pharmaceutical composition of the invention can be prepared into various dosage forms as needed.Including but not limited to, percutaneous, mucous membrane, nose,
Buccal, the sublingual or oral tablet used, solution, granule, patch, paste, capsule, aerosol or suppository.
The administration method of pharmaceutical composition of the invention is unrestricted, as long as it can play desired therapeutic effect or prevention
Effect, including but not limited to intravenously, in peritonaeum, intraocularly, intra-arterial, intrapulmonary is taken orally, in vesicle, intramuscular, and tracheae
Interior, subcutaneous, local by pleura by skin, sucking, by mucous membrane, skin, stomach is intra-articular, intra-ventricle, directly
Intestines, vagina, in skull, in urethra, in liver, in tumor.In some cases, it can systematically be administered.It is office in some cases
Portion it is administered.
The dosage of pharmaceutical composition of the invention is unrestricted, as long as obtaining desired therapeutic effect or preventive effect i.e.
Can, appropriate determination can be carried out according to symptom, gender, age etc..Therapeutic agent composition of the invention or prophylactic agent combination
The dosage of object, which can be used, for example determines the therapeutic effect of disease or preventive effect as index.
The present invention also provides application of the mentioned-above long-chain non-coding RNA in the drug of preparation treatment liver cancer.
The present invention also provides application of the mentioned-above inhibitor in the drug of preparation treatment liver cancer.
The present invention also provides a kind of methods of diagnosing liver cancer, and described method includes following steps:
(1) sample of subject is obtained；
(2) expression of LINC01876 in Samples subjects is detected；
(3) it associates whether by the expression of the LINC01876 measured with the illness of subject.
(4) compared with normal control, the expression of LINC01876 is significantly increased, then the subject is judged with liver
Cancer judges that risk of the subject with liver cancer is high or liver cancer patient is judged as recurrence or liver cancer patient is judged
For prognosis mala.
The present invention also provides a kind for the treatment of method of liver cancer, the method includes inhibit LINC01876 expression quantity or
Inhibit the adjusting activity of LINC01876.
The present invention also provides a kind of screening techniques of tumour medicine, can be by after adding testing drug to cancer cell
Or some period after applying testing drug to tumor model animal measures the expression of LINC01876 to measure tumour medicine
The effect of object improvement tumor prognosis.More specifically, when the expression of LINC01876 drops after adding or applying testing drug
When low or when restoring normal level, the drug may be selected as the therapeutic agent for improving tumor prognosis.
In the context of the present invention, " diagnosing liver cancer " include judge subject whether suffered from liver cancer, judge it is tested
Person, which whether there is, to be suffered from the risk of liver cancer, judges whether liver cancer patient has recurred and shifted, judges that liver cancer patient controls drug
The reactivity for the treatment of or the prognosis situation for judging liver cancer patient.
" treatment " used herein is covered treatment-related in such as mankind of the mammal with related disease or illness
Disease or morbid state, and include:
(1) prevent disease or morbid state occurs in mammals, especially when the mammal is susceptible in the disease
Diseased state, but when being not yet diagnosed with this morbid state；
(2) inhibit disease or morbid state, that is, prevent its generation；Or
(3) alleviate disease or morbid state, even if disease or morbid state subside.
Term " treatment " is usually directed to treatment mankind or animal (for example, being applied by animal doctor), wherein can reach certain pre-
The therapeutic effect of phase, for example, inhibiting the development (including reduce development speed, stop development) of illness, improving illness and healing
Illness.It further include the treatment as precautionary measures (such as prevention).To not yet development be illness but have development be the illness endanger
The purposes of the patient of danger, is also included in term " treatment ".
The advantages of the present invention:
The molecular marker for having found a kind of diagnosing liver cancer of the invention can be occurred using the molecular marker in liver cancer
Early stage can be used as judging, provide the survival rate of patient.
Detailed description of the invention
Fig. 1 shows the statistical chart of the differential expression situation using QPCR detection LINC01876.
Specific embodiment
The present invention is described in further detail with reference to the accompanying drawings and examples.Following embodiment is merely to illustrate this
It invents rather than limits the scope of the invention.Test method without specific conditions in embodiment, usually according to conventional strip
Part, such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring HarborLaboratory
Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.
Embodiment 1 screens the non-long-chain coding RNA of differential expression
1, it draws materials:
The operation excision cancerous tissue of 5 primary hepatic carcinoma patients and cancer beside organism are as experiment sample.All equal arts of cancerous tissue
Proved by pathology is liver cancer afterwards.The preoperative non-row Radiotherapy chemotherapy of whole primary hepatic carcinoma patients, all cases complete clinical data.It is all
Patient endorsed informed consent form.
2, step:
(1) tissue specimen total serum IgE is extracted using TRIzol reagent, and with RNasey Mini Kit purification
RNA；
(2) using QuickAmp Labeling Kit, One-Color (Agilent p/n 5190-0442) synthesis, mark
Remember double-strand cDNA；
(3) hybridize after the double stranded cDNA purification marked in the Human 8x60K LncRNA of Arraystar company
Expression array information chip；
(4) it is scanned after hybridization wash by Agilent Microarray Scanner (Agilent p/n G2565BA)
Instrument is scanned analysis；
(5) primary data analysis is completed by Agilent Feature Extraction Software software, differential gene
Select to use pairing Random variance model method, the standard of differential gene is variation expression 2 times or more and P value in cancerous tissue
≤0.05。
3, result
Sequencing result is shown: compared with cancer beside organism, differential expression LncRNA is 478 in liver cancer tissue, wherein raising
It is 301, downward is 177.
2 large sample of embodiment verifies the differential expression LncRNA filtered out
Based on the sequencing of chip early period as a result, according to the size of P value, we select LINC01876 to verify.
1, sample collection
Liver cancer tissue and its each 30 of corresponding cancer beside organism are collected according to the method for embodiment 1.
2, it is verified in mRNA level in-site
Reagent: reverse transcription reagent box (DDR037A) is purchased from precious bioengineering (Dalian) Co., Ltd.Real-time (the Real- of fluorescence
Time) SYBR Premix Ex Taq used in quantitative PCR (polymerase chain reaction)TM(Tli RNaseH
Plus) kit is the production of Takara company of Japan.
2.1 extract tissue RNA
Step is the same as embodiment 1.
2.2 reverse transcription
With the total serum IgE (1 μ g) of extraction for template, following reaction system is added, specifically:Buffer
4 μ L,1 μ L, Oligo dT Primer (50 μM) of RT Enzyme Mix, 1 μ L, Random 6mers (100 μM)
1 μ L, with the ddH of no RNA enzyme2O supplies reaction volume for 20 μ L.Above-mentioned mixed liquor is placed in 37 DEG C of 15min, 85 DEG C of 5s, i.e.,
Obtain cDNA.The cDNA can be used for lncRNA Real-time PCR detection.
2.3 QPCR
According to Japanese Takara companyPremix Ex TaqTM(Tli RNaseH Plus) kit explanation
Book is operated.
Reaction system: SYBR Premix Ex TaqTM(2 ×) 25 μ L, ROX Reference Dye (50 ×) 1 μ L, PCR
1 μ L, PCR downstream primer (10 μM) of upstream primer (10 μM), 14 μ L of μ L, cDNA, sterilize ddH2O 18μL。
Response procedures: 95 DEG C of 20s initial denaturations extend process circulation by 95 DEG C of 10s denaturation, 51 DEG C of 20s annealing, 70 DEG C of 10s
40 times, obtain Ct value.
As a result relative quantification method, formula 2 are used-△△ctIt calculates.Experiment is repeated 3 times.
Design of primers: according to LINC01876 transcript sequence, pass through the design of primers tool (Primer BLAST) of NCBI
Design primer, primer sequence are as follows: upstream primer: 5 '-GGTCAGAACACATAATACA-3 ' (SEQ ID NO.3)；Under
Swim primer: 5 '-AGAGGCATTCCAATAATC-3 ' (SEQ ID NO.4).
According to GAPDH (reference gene) primers, upstream primer: 5 '-CTCTGGTAAAGTGGATATTGT-3 '
(SEQ ID NO.5)；5'-GGTGGAATCATATTGGAACA-3'(SEQ ID NO.6).
3, result
The results show that there is LINC01876 level in 27 cancerous tissues to be significantly higher than cancer beside organism in 30 cancerous tissues.Statistics
As a result as shown in Figure 1, compared with cancer beside organism, LINC01876 is horizontal significantly raised in liver cancer tissue, and difference is anticipated with statistics
Adopted (P < 0.05 *).
The explanation of above-described embodiment is only intended to understand method and its core concept of the invention.It should be pointed out that for this
For the those of ordinary skill in field, without departing from the principle of the present invention, several improvement can also be carried out to the present invention
And modification, these improvement and modification will also be fallen into the protection scope of the claims in the present invention.
Sequence table
<110>Shandong ProvinceQianfoshan Hospital
<120>application of the LINC01876 as the molecular marker of diagnosing liver cancer
<160> 6
<170> SIPOSequenceListing 1.0
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<213>source of people (Homo sapiens)
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ccgagccagg tgcggcttat aatctcgtgg tgcgccgttt tttaagccgg tcggaaaagc 120
gcagtattcg ggtgggagtg acccgatttt ccagggatgg aagaagatac ttggaaaaat 180
cagggaagag tgaagaagat acttcaaaaa atcggggaag attttcatca taaggtccaa 240
gcaaagattc ctgagcctga gtctactgac aaatatacca catccccaga gtaagttgga 300
gtctcttaaa attgtcttgc tggcatctag cggagattgt ccccacaagc atgttcctta 360
tgacggatgc ctgggtcaga acacataata cattcctttt tataagcaca aagattctga 420
gaagcactgc ccctcccacg tgtcacactc tggggagaga ttattggaat gcctcttgga 480
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tgtttcaggt aatgtaacca gattttccag tgacttgtga attaacaggc taaaaactag 600
ttttcagttt ctggagaagg gttcccaatc tcatttgagg ctattggagg aaaaatccct 660
tcagaaaata aagcatgaca gtaagatttt agtatgcagg aagtaaattc agttcctttg 720
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gggttggacc aggaaattga gtgtagggtt ataggtgata agatgaggag aggcactccc 840
ctcaggagtt aagatgcagg aaatttggtt tgcactttag ccagtacaag gcatttcacc 900
aggatggaga atatgtgctc tcttgcacag aaatccgtgc cagcagtaag tgatgtggaa 960
ggatttagtg aaattttgcc aataacccca ggcttactgc ttaatgaaca gaacattctc 1020
ctgggacttg aagaggtcct atgaaataag ggacataaat gatgtacttt cttttctgtt 1080
aggcttaaga aattctgttc tgagtgcaaa tagagggaat gatttccgac tttcctatta 1140
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aacctagtca gtcaattgat ttattagaat tcctggaaga agtctgagta aacacaatct 1260
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aaatgaaaca gtgcaatgta aaactagtat aatgatggtc gagagtaggt ccccaataaa 1380
tcttggttat tactgttatt ggagagaatg atgaaattta aagctagtgg gggaaaaaga 1440
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tcagtaccct cagtaaatca gagttgctgt gacctgggct ttgatgtaag ggtagcagaa 1560
tgatttagaa aaaacagcat tagattaaaa gccagagaca tattatagtc ctagttcttt 1620
cgcttactag agatttgacc ttgaaaagct taatttgttt aaatcccgtt tcctcatctg 1680
aaaaatgaag actgatgata tctgtcctaa ctccatcttg tgatgatcca atggaataaa 1740
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<213>source of people (Homo sapiens)
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gcagtttgat ctcagactgc tgtgctagca atcagcgaga ctccctgtga gtaggaccct 60
ccgagccagg tgcggcttat aatctcgtgg tgcgccgttt tttaagccgg tcggaaaagc 120
gcagtattcg ggtgggagtg acccgatttt ccagtgaata agaatggtct tcttacataa 180
tgcagggatg gaagaagata cttggaaaaa tcagggaaga gtgaagaaga tacttcaaaa 240
aatcggggaa gattttcatc ataaggtcca agcaaaggca tgagtataag atgtgtattc 300
ctgagcctga gtctactgac aaatatacca catccccaga gtaagttgga gtctcttaaa 360
attgtcttgc tggcatctag cggagattgt ccccacaagc atgttcctta tgacggatgc 420
ctgggtcaga acacataata cattcctttt tataagcaca aagattctga gaagcactgc 480
ccctcccacg tgtcacactc tggggagaga ttattggaat gcctcttgga tcaggtatct 540
ttggtgatca ttccacctag ttaagatgaa gctggtgata gcctttggct tgtttcaggt 600
aatgtaacca gattttccag tgacttgtga attaacaggc taaaaactag ttttcagttt 660
ctggagaagg gttcccaatc tcatttgagg ctattggagg aaaaatccct tcagaaaata 720
aagcatgaca gtaagatttt agtatgcagg aagtaaattc agttcctttg gagatcagca 780
tgcctctatt caatcctctc cttaatccct tatgagtcag atctagtaga gggttggacc 840
aggaaattga gtgtagggtt ataggtgata agatgaggag aggcactccc ctcaggagtt 900
aagatgcagg aaatttggtt tgcactttag ccagtacaag gcatttcacc aggatggaga 960
atatgtgctc tcttgcacag aaatccgtgc cagcagtaag tgatgtggaa ggatttagtg 1020
aaattttgcc aataacccca ggcttactgc ttaatgaaca gaacattctc ctgggacttg 1080
aagaggtcct atgaaataag ggacataaat gatgtacttt cttttctgtt aggcttaaga 1140
aattctgttc tgagtgcaaa tagagggaat gatttccgac tttcctatta gatagcagat 1200
atctttgcat cttggataca tttagaaaga atagaaatgt gaatgattga aacctagtca 1260
gtcaattgat ttattagaat tcctggaaga agtctgagta aacacaatct cattctcttt 1320
ctttttctct ctgtcagttc ttcttcttgg gttcctatac tatgggatat aaatgaaaca 1380
gtgcaatgta aaactagtat aatgatggtc gagagtaggt ccccaataaa tcttggttat 1440
tactgttatt ggagagaatg atgaaattta aagctagtgg gggaaaaaga atcgtacaaa 1500
ctggaaatga attggaatga gtgttgcttc aggttgccct caatttggta tcagtaccct 1560
cagtaaatca gagttgctgt gacctgggct ttgatgtaag ggtagcagaa tgatttagaa 1620
aaaacagcat tagattaaaa gccagagaca tattatagtc ctagttcttt cgcttactag 1680
agatttgacc ttgaaaagct taatttgttt aaatcccgtt tcctcatctg aaaaatgaag 1740
actgatgata tctgtcctaa ctccatcttg tgatgatcca atggaataaa gtgctgtcaa 1800
aatgtgaaaa aaaaaaaaaa aaa 1823
<210> 3
<211> 19
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 3
ggtcagaaca cataataca 19
<210> 4
<211> 18
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 4
agaggcattc caataatc 18
<210> 5
<211> 21
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 5
ctctggtaaa gtggatattg t 21
<210> 6
<211> 20
<212> DNA
<213>artificial sequence (Artificial Sequence)
<400> 6
ggtggaatca tattggaaca 20
Claims (10)
1. detecting application of the reagent of long-chain non-coding RNA expression in preparation diagnosis for liver cancer or prognosis prediction product；Institute
State the encoding gene Gene ID:101929378 of long-chain non-coding RNA.
2. application according to claim 1, which is characterized in that the long-chain non-coding RNA is LINC01876.
3. application according to claim 1 or 2, which is characterized in that the reagent is including the use of SYBR Green, TaqMan
Probe, molecular beacon, double cross probe or combined probe detect the PCR amplification used when the long-chain non-coding RNA expression quantity
Primer.
4. application according to claim 3, which is characterized in that the primer sequence such as SEQ ID NO.2 and SEQ ID
Shown in NO.3.
5. a kind of for diagnosis for liver cancer or the product of prognosis prediction, which is characterized in that the product includes that detection right is wanted
The reagent of the expression of long-chain non-coding RNA described in asking 1 or 2.
6. product according to claim 5, which is characterized in that the reagent includes SYBR Green, TaqMan probe, divides
Sub- beacon, double cross probe or combined probe detect the PCR amplification primer used when the long-chain non-coding RNA expression quantity.
7. product according to claim 6, which is characterized in that the primer sequence such as SEQ ID NO.2 and SEQ ID
Shown in NO.3.
8. a kind of for treating the pharmaceutical composition of liver cancer, which is characterized in that described pharmaceutical composition includes claims 1 or 2
The inhibitor of the long-chain non-coding RNA.
9. product according to claim 8, which is characterized in that the inhibitor includes inhibiting long-chain non-coding RNA horizontal
Reagent, or inhibit the reagent of the long-chain non-coding RNA functional activity.
10. application of the long-chain non-coding RNA of any of claims 1 or 2 in the drug of preparation treatment liver cancer.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811481731.7A CN109355391A (en) | 2018-12-05 | 2018-12-05 | Application of the LINC01876 as the molecular marker of diagnosing liver cancer |
| CN201911071179.9A CN110592226B (en) | 2018-12-05 | 2019-11-05 | Application of LINC01876 as molecular marker for diagnosing liver cancer |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811481731.7A CN109355391A (en) | 2018-12-05 | 2018-12-05 | Application of the LINC01876 as the molecular marker of diagnosing liver cancer |
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| CN109355391A true CN109355391A (en) | 2019-02-19 |
Family
ID=65331341
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| CN201811481731.7A Pending CN109355391A (en) | 2018-12-05 | 2018-12-05 | Application of the LINC01876 as the molecular marker of diagnosing liver cancer |
| CN201911071179.9A Active CN110592226B (en) | 2018-12-05 | 2019-11-05 | Application of LINC01876 as molecular marker for diagnosing liver cancer |
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| CN201911071179.9A Active CN110592226B (en) | 2018-12-05 | 2019-11-05 | Application of LINC01876 as molecular marker for diagnosing liver cancer |
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Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107201366A (en) * | 2017-06-02 | 2017-09-26 | 扬州大学 | A kind of analysis and preparation method for diagnosing cancer of liver with the antisense long-chain non-coding RNA for the treatment of |
| CN107213471A (en) * | 2016-09-09 | 2017-09-29 | 中国科学院生物物理研究所 | A kind of new detection of long-chain non-coding RNA and its application interacted for liver cancer and tumor microenvironment of hepatocellular carcinoma |
| CN107254521A (en) * | 2017-06-09 | 2017-10-17 | 中山大学附属第三医院 | lnc‑PCDH9‑13:Application of 1 detection reagent in reagent/kit of diagnosing cancer of liver is prepared |
| CN107267625A (en) * | 2017-07-06 | 2017-10-20 | 王冬国 | Purposes of the lncRNA as biomarker in liver cancer diagnosis and treatment |
| CN108546702A (en) * | 2018-04-10 | 2018-09-18 | 西安交通大学 | The siRNA for targeting long-chain non-coding RNA DDX11-AS1 and its application in liver cancer treatment |
| CN108588229A (en) * | 2018-07-13 | 2018-09-28 | 山东省千佛山医院 | Applications of the LINC01703 as the molecular marker of diagnosing liver cancer |
| US20180305689A1 (en) * | 2015-04-22 | 2018-10-25 | Mina Therapeutics Limited | Sarna compositions and methods of use |
| CN108728534A (en) * | 2018-05-23 | 2018-11-02 | 王辉云 | 4-LncRNA molecular labels are used for the kit of prognosis in hcc assessment |
| CN108753969A (en) * | 2018-06-13 | 2018-11-06 | 北京泱深生物信息技术有限公司 | Application of the long-chain non-coding RNA in hepatocellular carcinoma diagnosis and treatment |
| WO2018204764A1 (en) * | 2017-05-05 | 2018-11-08 | Camp4 Therapeutics Corporation | Identification and targeted modulation of gene signaling networks |
| CN108823305A (en) * | 2017-04-28 | 2018-11-16 | 青岛市中心医院 | A kind of multiple PCR method of 8 kinds of tumour correlation long-chain non-coding RNAs of synchronous detection |
| CN108866187A (en) * | 2018-06-20 | 2018-11-23 | 宁波大学 | One kind long-chain non-coding RNA marker relevant to lung cancer auxiliary diagnosis and its application |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106995858B (en) * | 2017-06-01 | 2021-03-02 | 青岛泱深生物医药有限公司 | lncRNA related to liver cancer diagnosis and treatment |
-
2018
- 2018-12-05 CN CN201811481731.7A patent/CN109355391A/en active Pending
-
2019
- 2019-11-05 CN CN201911071179.9A patent/CN110592226B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20180305689A1 (en) * | 2015-04-22 | 2018-10-25 | Mina Therapeutics Limited | Sarna compositions and methods of use |
| CN107213471A (en) * | 2016-09-09 | 2017-09-29 | 中国科学院生物物理研究所 | A kind of new detection of long-chain non-coding RNA and its application interacted for liver cancer and tumor microenvironment of hepatocellular carcinoma |
| CN108823305A (en) * | 2017-04-28 | 2018-11-16 | 青岛市中心医院 | A kind of multiple PCR method of 8 kinds of tumour correlation long-chain non-coding RNAs of synchronous detection |
| WO2018204764A1 (en) * | 2017-05-05 | 2018-11-08 | Camp4 Therapeutics Corporation | Identification and targeted modulation of gene signaling networks |
| CN107201366A (en) * | 2017-06-02 | 2017-09-26 | 扬州大学 | A kind of analysis and preparation method for diagnosing cancer of liver with the antisense long-chain non-coding RNA for the treatment of |
| CN107254521A (en) * | 2017-06-09 | 2017-10-17 | 中山大学附属第三医院 | lnc‑PCDH9‑13:Application of 1 detection reagent in reagent/kit of diagnosing cancer of liver is prepared |
| CN107267625A (en) * | 2017-07-06 | 2017-10-20 | 王冬国 | Purposes of the lncRNA as biomarker in liver cancer diagnosis and treatment |
| CN108546702A (en) * | 2018-04-10 | 2018-09-18 | 西安交通大学 | The siRNA for targeting long-chain non-coding RNA DDX11-AS1 and its application in liver cancer treatment |
| CN108728534A (en) * | 2018-05-23 | 2018-11-02 | 王辉云 | 4-LncRNA molecular labels are used for the kit of prognosis in hcc assessment |
| CN108753969A (en) * | 2018-06-13 | 2018-11-06 | 北京泱深生物信息技术有限公司 | Application of the long-chain non-coding RNA in hepatocellular carcinoma diagnosis and treatment |
| CN108866187A (en) * | 2018-06-20 | 2018-11-23 | 宁波大学 | One kind long-chain non-coding RNA marker relevant to lung cancer auxiliary diagnosis and its application |
| CN108588229A (en) * | 2018-07-13 | 2018-09-28 | 山东省千佛山医院 | Applications of the LINC01703 as the molecular marker of diagnosing liver cancer |
Non-Patent Citations (1)
| Title |
|---|
| 陈娟等: "lncRNA在绝经后骨质疏松症肾阴虚证中的表达特征及调控网络分析", 《中国骨质疏松杂志》 * |
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| Publication number | Publication date |
|---|---|
| CN110592226B (en) | 2020-08-11 |
| CN110592226A (en) | 2019-12-20 |
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