CN109136381A - A kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung and its application - Google Patents
A kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung and its application Download PDFInfo
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Abstract
The invention belongs to technical field of biomedical detection, are in particular related to tRNA-Leu-CAG as the application in the molecular marker of diagnosis and treatment adenocarcinoma of lung and preparation diagnosis adenocarcinoma of lung reagent or kit；A kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung and its application, including tRNA, the extraction step of the tRNA are as follows: tissue RNA extractions, the demethylation of RNA, RNA precipitate, RNA reverse transcription are at cDNA, tRNA qPCR array detection and data processing.
Description
Technical field
The invention belongs to technical field of biomedical detection, and in particular to a kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung
And its application.
Background technique
Lung cancer is one of whole world disease incidence and the highest malignant tumour of case fatality rate.Recently, adenocarcinoma of lung gradually replaces lung squama
Cancer becomes the most common histological type in lung cancer.And adenocarcinoma of lung due to its subtypes difference and comprising driving gene it is prominent
The difference of change, patient survival difference are huge.With the appearance of gene sequencing technology and the exploitation of targeted drug, lung cancer patient
Prognosis have and be obviously improved, but overall 5 years survival rates are still undesirable.
In recent years, effect of the non-coding RNA in tumour is also gradually reported, and tRNA is the most abundant as intracellular level
Non-coding RNA, major function are that the amino acid of Mobilization participates in Protein synthesis.The research heat in early stage tRNA field
Point be concentrated mainly on that its structure, processing is mature and the interaction of aminoacyl tRNA synthetase on, with going deep into for research,
The biological function of tRNA gradually shows diversity.Experimental evidence shows that tRNA is not passively amino acid transport to just
On the peptide chain of extension, but can body stress during active performance regulating and controlling effect, or even can be according to extracellular
The change of nutrient environment drive in the wrong direction back nucleus participate in cell gene expression regulation.Moreover, the proliferation of cell, differentiation and
Apoptotic process is all along with the change in the library tRNA and the variation of tRNA expression.TRNA aggregate level keeps permanent in the cell
In the case where fixed, tRNA can also realize the accuracy controlling to gene by changing its load level.Since MTTL1 (mt-
TRNALeu (UUR)) point mutation and MELAS syndrome relationship be found since, the relationship of tRNA and disease is also by people
Pay close attention to.Nearest one studies have shown that the overexpression of specific tRNA can drive the expression of specific oncogene to promote cream
The progress and transfer of gland cancer.More it is disclosed as that we provide " kill " tumour cells some researches show that, tRNA critical function
New method.Applicant has found that tRNA-Leu-CAG is expressed in pulmonary adenocarcinoma with respect to normal lung tissue's height, and body under study for action
Inside and outside experiment shows that the tRNA can promote the proliferation of lung adenocarcinoma cell.Currently, in relation in normal lung tissue and pulmonary adenocarcinoma
TRNA quantitative analysis does not have research, and the variation of tRNA-Leu-CAG expression quantity causes the variation of adenocarcinoma of lung biological function
Correlative study is also or blank.And there has been no the complete reagents for detecting tRNA-Leu-CAG expression in the tissue
Box.
Summary of the invention
The purpose of the present invention is to provide a kind of tRNA markers of diagnosis and treatment adenocarcinoma of lung, and another object of the present invention is to mention
For the application in tRNA-Leu-CAG correlation adenocarcinoma of lung diagnostic kit.
To achieve the above object, the invention provides the following technical scheme: a kind of 1. tRNA molecular markers of diagnosis and treatment adenocarcinoma of lung
The extraction step of object and its application, including tRNA, the tRNA is as follows: tissue RNA extraction, the demethylation of RNA, RNA precipitate,
RNA reverse transcription is detected at cDNA, tRNA qPCR array and data processing.
2. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, the tissue
RNA extraction step needs to choose 50 pairs of pulmonary adenocarcinomas and Ai Pang normal lung tissue, and tissue samples are diagnosed as lung from thoracic surgery
Gland cancer, and carry out the patient of operation excision；Taken tissue block is coated with using masking foil, is placed in tissue freezing pipe, and
It is placed in liquid nitrogen and saves immediately, extraction step is as follows:
(1) pre-cooling tissue grinder instrument is to 4 DEG C；
(2) appropriate tissue (adenocarcinoma of lung/Carcinoma side normal tissue) is cut in the tissue grinder pipe added with zirconium pearl, and 500 μ are added
L NucLeoZOL is homogenized in tissue grinder instrument, is homogenized mode are as follows: is opened 30s, is suspended 1min, 4 circulations, if there is still there is block
Shape tissue is not ground, and can add a circulation；
(3) homogenate is added in new 1.5mL EP pipe, 200 μ L RNase-free water is added, mix well, room temperature
Stand 15min；
(4) 4 DEG C of low-temperature centrifugations, 12000g, 15min；
(5) it takes 520 μ L supernatants to be added in new 1.5mL EP pipe, 500 μ L buffer MX is added, mix well；
(6) NucleoSpin is added in 700 μ L mixed liquors, waste liquid is abandoned in 8000g, 30s centrifugation；
(7) NucleoSpin is added in residual mixed liquor, waste liquid is abandoned in 8000g, 30s centrifugation；
(8) 700 μ L buffer RX, 8000g, 30s centrifugations are added, abandon waste liquid；
(9) 350 μ L buffer RX, 8000g, 2min are added, waste liquid is abandoned in centrifugation；
(10) pillar is placed in new 1.5mL EP pipe, uncaps and dries 5min, 50 μ LRNase-free water are added, incubate
Educate 1min；
(11) 11000g, 2min, 4 DEG C of low-temperature centrifugations collect the liquid being centrifuged, 2 μ L are taken to be detected with NanoDrop2000
The concentration and purity (A260/A280, A260/A230) of RNA.
3. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, the RNA's
The concrete operations of demethylation step are as follows:
(1) selection total concentration is greater than 40ng/ μ L, A260/A280 between 1.8 to 2.0, and A260/A230 is greater than 1.7 sample
Product carry out demethylation processing；
(2) demethylation mix is prepared according to following table:
(3) demethylation condition: 37 DEG C of water bath with thermostatic control 100min；It terminates methylation conditions: 160 μ L Nuclease- is added
Free water and 40 μ L Stop buffer (5X), mix well.
4. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, the RNA is heavy
The operating method of shallow lake step is as follows:
(1) 400 μ L phenol chloroforms are added, mix well, are incubated at room temperature 10min, then 12000rpm is centrifuged 10min；
(2) it takes supernatant to be placed in new 1.5mL EP pipe, 400 μ L chloroforms is added, mix well, then 12000rpm is centrifuged
10min；
(3) it takes supernatant to be placed in new 1.5mL EP pipe, 1mL isopropanol is added, mixes well, is stored at room temperature 10min, so
12000rpm is centrifuged 10min afterwards；
(4) it discards supernatant, is added 75% ethyl alcohol of 1mL (preparation of DEPC water), piping and druming washing；
(5) 7500rpm, 4 DEG C of centrifugation 5min, discards supernatant；
(6) uncap air-dried 5-10min；
(7) 11 μ L Nuclease-free water are added, places 10min in 56 DEG C of water-baths, RNA is made to be substantially soluble in water.
5. the tRNA molecular marker and its application, the RNA of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1 are anti-
The operating method for being transcribed into cDNA step is as follows:
(1) annealing mixture is prepared by following system:
(2) it is placed in PCR instrument, reaction condition: 65 DEG C, 5min, be immediately placed on ice, cooling 1min or more；
(3) mix is made by following system:
(4) the 2nd is mixed well with the 3rd solution, 25 DEG C of incubation 8min, then 50 DEG C of incubation 50min；
(5) 85 degrees Celsius of incubation 5min terminate reaction, and place the product in cooled on ice.
6. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, the tRNA
The operating method of qPCR array detecting step is as follows:
(1) sample of the selection preliminary experiment Ct value less than 25 carries out the detection of PCR array；
(2) 1:40 dilutes cDNA, mixes well；
(3) it prepares GDC Control:1.5 μ L and does not invert RNA+7.5 μ L SYBR Green Master Mix+6 μ L
Nuclease-Free water；
(4) Blank Control:20 μ L SYBR Green Master Mix+20 μ L Nuclease-Free water is prepared；
(5) reaction system is prepared:
(6) sample is added to 384 orifice plates as requested；
(7) it is centrifuged using horizontal centrifuge, condition: 1500 revs/min, the time: 3 minutes.Confirm well bubble-free
Afterwards, qPCR detection is carried out according to following procedure:
7. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, the data
The operating method of processing step is such as are as follows: data obtained need to carry out first step standardization between different chips, set
Markization coefficient, value >=35 Ct are deemed to be equivalent to 35 processing, and qPCR data handling procedure is as follows:
Δ Δ Ct=Δ Ct (sample)-Δ Ct (internal reference U6)
Fold difference=2- Δ Δ Ct (tumour)/2- Δ Δ Ct (normal)
The difference selection compared between two groups is examined with sided t, when p value < 0.05, it is believed that have statistical difference；
As a result: tRNA quantitative detection result in tissue is depicted as thermal map (Fig. 1) by applicant, by comparing tissue sample in pairs
It is found after tRNA expression quantity in this, tRNA-Leu-CAG is that opposite Ai Pang normal lung tissue height expression is most aobvious in pulmonary adenocarcinoma
The tRNA (Fig. 2) (p < 0.05) of work
Compared with prior art, the beneficial effects of the present invention are:
1, the present invention provides application of the tRNA-Leu-CAG expression in adenocarcinoma of lung diagnosis, this hairs in detection tissue
TRNA in bright for function assessment experiment is tRNA-Leu-CAG-1 (Fig. 3), and being overexpressed/strike the internal reference that inefficient detection uses is
U6, institute are using sequence
F:5'-CTCGCTTCGGCAGCACA-3'；
R:5'-AACGCTTCACGAATTTGCGT-3'
The primer sequence of tRNA-Leu-CAG is purchased from Arraystar company.
The present invention carries out functional study for the apparent tRNA-Leu-CAG of two groups of differential tissue expressions, shows it to lung
Influence caused by adenocarcinoma cell proliferation；
In one embodiment of the invention, the tRNA-Leu-CAG is provided in preparing pulmonary cancer diagnosis kit
Application.
The present invention provides the sequence of detected tRNA-Leu-CAG, internal control primer sequence, targeted tumor type is
Adenocarcinoma of lung.
2, the present invention be it is first by tRNA-Leu-CAG express based on and the kit that develops.
Application of the tRNA-Leu-CAG in preparation pulmonary adenocarcinoma detection kit, is to prepare energy in conventional manner
The primer of specific amplification tRNA-Leu-CAG further includes first in the diagnostic reagent or kit in addition to specific primer
Base enzyme, demethylation buffer, PCR reaction solution, PCR reaction solution is by SYBR Green dyestuff, dNTP, Mg2+, DTT, reversion
Record the composition such as enzyme and Buffer.Each component and dosage are common knowledge for one of ordinary skill in the art in PCR reaction solution；
Whether the expression of tRNA-Leu-CAG is abnormal in vitro detection pulmonary adenocarcinoma, is that detection osteosarcoma to be measured is thin first
The expression quantity of tRNA-Leu-CAG, the followed by expression quantity with the tRNA-Leu-CAG in normal cancer side are compared in born of the same parents' tissue
Compared with finally judging whether this nucleic acid molecules marker has up-regulated expression in pulmonary adenocarcinoma to be measured.
Detailed description of the invention
Attached drawing is used to provide further understanding of the present invention, and constitutes part of specification, with reality of the invention
It applies example to be used to explain the present invention together, not be construed as limiting the invention.In the accompanying drawings:
Fig. 1 is to detect the thermal map that lung 50 expresses tRNA in gland cancer and its Ai Pang normal lung tissue using tRNA chip.
LC represents pulmonary adenocarcinoma, and N represents Ai Pang normal lung tissue, and same digital number, which represents, comes from same patient, each vertical setting of types generation
A kind of tRNA of table, totally 88 kinds.
Fig. 2 is tRNA-Leu-CAG expression statistical chart in adenocarcinoma of lung and its Ai Pang normal lung tissue.Visual tumors
The expression of tRNA-Leu-CAG is apparently higher than lung tissue by cancer in tissue.
Fig. 3 is to study used tRNA-Leu-CAG-1 secondary structure schematic diagram for function assessment in the present invention.
Fig. 4 is that pCDH-Leu-CAG is overexpressed Efficiency testing.Since tRNA is the highest non-coding of cell inner expression abundance
RNA, therefore be coated with virus by plasmid and realize overexpression limited efficacy, being successfully overexpressed tRNA efficiency is about 2-3 times or so.
Fig. 5 is the curve graph that tRNA-Leu-CAG is overexpressed the influence being proliferated to lung adenocarcinoma cell.In lung adenocarcinoma cell
TRNA-Leu-CAG is overexpressed, and can dramatically increase the proliferative capacity of lung adenocarcinoma cell.
Fig. 6 is influence of the tRNA-Leu-CAG overexpression to the subcutaneous one-tenth knurl ability of lung adenocarcinoma cell.Left figure is subcutaneous tumor formation
Nude mice model, right figure be tRNA-Leu-CAG be overexpressed compared with nude mice of control group subcutaneous tumor volumes.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments the reality
It applies example and is only to aid in the understanding present invention, should not be regarded as a specific limitation of the invention, experiment as used in the following examples
Method is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
Embodiment 1:tRNA-Leu-CAG is overexpressed
Fig. 1-6 is please referred to, the present invention is the following technical schemes are provided: 1. building plasmids
This stage is pCDH using the carrier of overexpression, with puro resistance, is tested in the present invention for biological function
TRNA-Leu-CAG sequence is (Fig. 3): 5'-GTCAGGATGGCCGAGCGGTCTAAGGCGCTGCGTTCAGGTCGCAGTCTCC
CCTGGAGGCGTGGGTTCGAATCCCACTCCTGACA-3'；
Primer U6 sequence are as follows:
F:5'-CTCGCTTCGGCAGCACA-3 '；
R:5'-AACGCTTCACGAATTTGCGT-3'。
2, packet virus and infection cell
(1), 293T cell is spread into 6 orifice plates, when cell it is long to about 60% when prepare packet virus；
(2), prepare plasmid plasmid, packaging plasmid matches liquid
(3), liquid is changed after 6 hours, observes intracellular membranes distribution of particles situation.
(4), viral (safety cabinet operation) is received after 48 hours, collected virus liquid using syringe, and pass through filter membrane mistake
Filter.
(5) aim cell is spread into 6 orifice plates, 500 μ L viruses is taken to be infected；It changes liquid afterwards for 24 hours, is added in training base
Puromycin cultivates 24-48h, observes efficiency of infection and passes on.
3, detection is overexpressed efficiency
(1), logarithmic growth phase cell is tested.Cell training base is discarded, appropriate PBS washing；
(2), 500 μ LNucLeoZOL are added in Tissue Culture Dish, sufficiently piping and druming to cell cracking；
(3), conventional method extracts cell total rna, and the concentration and purity of RNA are detected using NanoDrop 2000；
(4), demethylation reverse transcription step is the same, detects tRNA-Leu-CAG according to PCR is carried out after 1:40 dilution proportion
Expression quantity；
4, result: being overexpressed in lung adenocarcinoma cell as shown in figure 4, pCDH-tRNA-Leu-CAG can succeed, expression
Difference has statistical significance.
Embodiment 2: cell proliferation experiment
1, cell is taken out from cell incubator, is opened in cell room super-clean bench, base will be trained using vacuum extractor
It is sucked out, is washed 2 times with PBS, appropriate pancreatin is added to crack, training base is then added and terminates reaction, attached cell is resuspended in sufficiently piping and druming, will
Cell is transferred in 15mL centrifuge tube, 800rpm, is centrifuged 5min, is discarded supernatant, and takes appropriate progress after adding 3mL training base to be sufficiently resuspended
Cell count；
2, enter 2000 cells in 96 orifice plate middle berths, 5 secondary orifices are arranged in each sample of every block of plate, and the hole around sample is added
200 μ L aqua sterilisas amount to 5 piece of 96 orifice plate；
3, one piece of 96 orifice plate is taken out daily, and training base is sucked out, the Pei Ji (1:10) containing CCK8 is added, carries out extinction after cultivating 1h
Degree detection (450nm)；
4, data processing: drawing cell growth curves figure, the use of software is excel and graphpad.Final result is such as
Shown in Fig. 5, it is seen that lung adenocarcinoma cell proliferative capacity can be remarkably reinforced in tRNA-Leu-CAG.
Finally, it should be noted that the foregoing is only a preferred embodiment of the present invention, it is not intended to restrict the invention,
Although the present invention is described in detail referring to the foregoing embodiments, for those skilled in the art, still may be used
To modify the technical solutions described in the foregoing embodiments or equivalent replacement of some of the technical features.
All within the spirits and principles of the present invention, any modification, equivalent replacement, improvement and so on should be included in of the invention
Within protection scope.
Claims (7)
1. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung, including tRNA, it is characterised in that: the tRNA's mentions
Take that steps are as follows: tissue RNA extraction, the demethylation of RNA, RNA precipitate, RNA reverse transcription are at cDNA, tRNA qPCR array
Detection and data processing.
2. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
State that tissue RNA extraction step needs to choose 50 pairs of pulmonary adenocarcinomas and Ai Pang normal lung tissue, tissue samples are examined from thoracic surgery
Break as adenocarcinoma of lung, and carries out the patient of operation excision；Taken tissue block is coated with using masking foil, is placed in tissue freezing pipe
It is interior, and be placed in liquid nitrogen save immediately, extraction step is as follows:
(1) pre-cooling tissue grinder instrument is to 4 DEG C；
(2) appropriate tissue (adenocarcinoma of lung/Carcinoma side normal tissue) is cut in the tissue grinder pipe added with zirconium pearl, and 500 μ L are added
NucLeoZOL is homogenized in tissue grinder instrument, is homogenized mode are as follows: is opened 30s, is suspended 1min, 4 circulations, if there is still there is bulk
Tissue is not ground, and can add a circulation；
(3) homogenate is added in new 1.5mL EP pipe, 200 μ L RNase-free water is added, mixes well, is stored at room temperature
15min；
(4) 4 DEG C of low-temperature centrifugations, 12000g, 15min；
(5) it takes 520 μ L supernatants to be added in new 1.5mL EP pipe, 500 μ L buffer MX is added, mix well；
(6) NucleoSpin is added in 700 μ L mixed liquors, waste liquid is abandoned in 8000g, 30s centrifugation；
(7) NucleoSpin is added in residual mixed liquor, waste liquid is abandoned in 8000g, 30s centrifugation；
(8) 700 μ L buffer RX, 8000g, 30s centrifugations are added, abandon waste liquid；
(9) 350 μ L buffer RX, 8000g, 2min are added, waste liquid is abandoned in centrifugation；
(10) pillar is placed in new 1.5mL EP pipe, uncaps and dries 5min, 50 μ L RNase-free water are added, be incubated for
1min；
(11) 11000g, 2min, 4 DEG C of low-temperature centrifugations collect the liquid being centrifuged, and 2 μ L is taken to detect RNA with NanoDrop 2000
Concentration and purity (A260/A280, A260/A230).
3. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
The concrete operations for stating the demethylation step of RNA are as follows:
(1) selection total concentration be greater than 40ng/ μ L, A260/A280 between 1.8 to 2.0, A260/A230 greater than 1.7 sample into
The processing of row demethylation；
(2) demethylation mix is prepared according to following table:
(3) demethylation condition: 37 DEG C of water bath with thermostatic control 100min；It terminates methylation conditions: 160 μ L Nuclease-free is added
Water and 40 μ L Stop buffer (5X), mix well.
4. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
The operating method for stating RNA precipitate step is as follows:
(1) 400 μ L phenol chloroforms are added, mix well, are incubated at room temperature 10min, then 12000rpm is centrifuged 10min；
(2) it takes supernatant to be placed in new 1.5mL EP pipe, 400 μ L chloroforms is added, mix well, then 12000rpm is centrifuged
10min；
(3) it takes supernatant to be placed in new 1.5mL EP pipe, 1mL isopropanol is added, mixes well, is stored at room temperature 10min, then
12000rpm is centrifuged 10min；
(4) it discards supernatant, is added 75% ethyl alcohol of 1mL (preparation of DEPC water), piping and druming washing；
(5) 7500rpm, 4 DEG C of centrifugation 5min, discards supernatant；
(6) uncap air-dried 5-10min；
(7) 11 μ L Nuclease-free water are added, places 10min in 56 DEG C of water-baths, RNA is made to be substantially soluble in water.
5. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
The operating method that RNA reverse transcription is stated into cDNA step is as follows:
(1) annealing mixture is prepared by following system:
(2) it is placed in PCR instrument, reaction condition: 65 DEG C, 5min, be immediately placed on ice, cooling 1min or more；
(3) mix is made by following system:
(4) the 2nd is mixed well with the 3rd solution, 25 DEG C of incubation 8min, then 50 DEG C of incubation 50min；
(5) 85 degrees Celsius of incubation 5min terminate reaction, and place the product in cooled on ice.
6. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
The operating method for stating tRNA qPCR array detecting step is as follows:
(1) sample of the selection preliminary experiment Ct value less than 25 carries out the detection of PCR array；
(2) 1:40 dilutes cDNA, mixes well；
(3) it prepares GDC Control:1.5 μ L and does not invert RNA+7.5 μ L SYBR Green Master Mix+6 μ L
Nuclease-Free water；
(4) Blank Control:20 μ L SYBR Green Master Mix+20 μ L Nuclease-Free water is prepared；
(5) reaction system is prepared:
(6) sample is added to 384 orifice plates as requested；
(7) it is centrifuged using horizontal centrifuge, condition: 1500 revs/min, the time: 3 minutes.After confirming well bubble-free, press
QPCR detection is carried out according to following procedure:
7. tRNA molecular marker and its application of a kind of diagnosis and treatment adenocarcinoma of lung according to claim 1, it is characterised in that: institute
State the operating method of data processing step such as are as follows: data obtained need to carry out at first step standardization between different chips
Reason sets markization coefficient, and value >=35 Ct are deemed to be equivalent to 35 processing, and qPCR data handling procedure is as follows:
Δ Δ Ct=Δ Ct (sample)-Δ Ct (internal reference U6)
Fold difference=2- Δ Δ Ct (tumour)/2- Δ Δ Ct (normal)
The difference selection compared between two groups is examined with sided t, when p value < 0.05, it is believed that have statistical difference；
As a result: tRNA quantitative detection result in tissue is depicted as thermal map (Fig. 1) by applicant, by comparing in tissue samples in pairs
TRNA expression quantity after find, tRNA-Leu-CAG be in pulmonary adenocarcinoma opposite Ai Pang normal lung tissue height express it is most significant
TRNA (Fig. 2) (p < 0.05).
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| CN201811310076.9A CN109136381A (en) | 2018-11-04 | 2018-11-04 | A kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung and its application |
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| CN201811310076.9A CN109136381A (en) | 2018-11-04 | 2018-11-04 | A kind of tRNA molecular marker of diagnosis and treatment adenocarcinoma of lung and its application |
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| EUKARYOTA等: "GenBank: HG983889.1", 《NCBI》 * |
| EUKARYOTA等: "GenBank: HG983889.1", 《NCBI》, 4 March 2015 (2015-03-04) * |
| MANQING LI: ""DN"DNA damage-Induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAsA damage-Induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAs", NAT STRUCT MOL BIOL, vol. 25, no. 11, XP036628336, DOI: 10.1038/s41594-018-0142-5 * |
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Inventor after: Zhang Huibiao Inventor after: Kuang Muyu Inventor after: Sun Yihua Inventor after: Zhou Zilang Inventor after: Li Duo Inventor after: Deng Chao Inventor before: Kuang Muyu Inventor before: Zhang Huibiao Inventor before: Sun Yihua Inventor before: Zhou Zilang Inventor before: Li Duo Inventor before: Deng Chao |