Application of miRNA-203a-3p to development of pancreatic cancer inhibiting drugs

1. The technology of mirna-203a-3p and pancreatic cancer, which is applied in the determination/testing of microorganisms, pharmaceutical formulations, compound screening/testing, etc., can solve the problems of limiting the scope of clinical application, low sensitivity and specificity, etc. To achieve the effect of promoting migration and transfer and improving the ability of invasion

Inactive Publication Date: 2020-07-10
NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Current pancreatic cancer biomarkers have relatively low sensitivity and specificity, limiting the scope of their clinical application

Method used

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  • Application of miRNA-203a-3p to development of pancreatic cancer inhibiting drugs
  • Application of miRNA-203a-3p to development of pancreatic cancer inhibiting drugs
  • Application of miRNA-203a-3p to development of pancreatic cancer inhibiting drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] 1.1 Screening of differentially expressed miRNAs

[0039] Log in to the Google Chrome browser, enter the URL: https: / / xenabrowser.net / datapages / , log in to the TCGA database, search for pancreatic cancer-related data packages to download, use the pheatmap package to analyze, and use the R language edgeR package to extract differential miRNAs. Select normal pancreatic tissue (normal Mean) and pancreatic cancer patient tissue (Tumor Mean) with a fold change (Fold Change) greater than 2 times, that is, logFC>2, and P<0.05, as miRNAs with statistically significant differential expression.

[0040] 1.2 Analysis of the conservation of differentially expressed miRNAs

[0041] Conservative analysis was carried out on the screened hsa-miR-192-5p (amino acid sequence such as SEQ ID NO: 2), hsa-miR-203a-3p and hsa-miR-451a (amino acid sequence such as SEQ ID NO: 3), Using miRBase and TargetScan websites to query its conservation, it was found that the gene sequences of hsa-miR-19...

Embodiment 2

[0115] Species conservative differentially expressed miRNAs survival curves and clinical stages

[0116] Analysis of differentially expressed and species-conserved miRNAs in pancreatic cancer tissues showed that their expression levels were correlated with patient survival. The results indicated that hsa-miR-192-5p, hsa-miR-203a-3p and hsa-miR-203a-3p in the high-expression group and hsa-miR-203a-3p in the low-expression group in pancreatic cancer patient tissues - The expression level of miR-451a was correlated with the survival rate of patients, and the result was statistically significant (P<0.05).

[0117] The miRNAs with statistically significant (P image 3 ).

Embodiment 3

[0119] Prediction of target gene outcome

[0120] Using DIANA TOOLS v5.0 biological information website to predict the target genes of hsa-miR-192-5p, hsa-miR-203a-3p with significant difference in high expression group and hsa-miR-451a with significant difference in low expression group, and according to the target gene Gene binding degree score to screen for target genes with higher scores.

[0121] Next, the correlation between the candidate target genes of miR-203a-3p and the survival of patients with pancreatic cancer was analyzed, and the results showed that the candidate target genes whose expression levels were correlated with patient survival and had statistical significance (P Figure 4 ). The research value of the positive correlation between miRNA and the target gene is small, so this topic only studies the target relationship with the negative correlation between the two.

[0122] Example 3

[0123]qRT-PCR verification of mRNA expression levels in HPNE cells, Bxp...

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Abstract

The present invention provides an application of miRNA-203a-3p to development of pancreatic cancer inhibiting drugs. 1) a model for screening the pancreatic cancer metastasis inhibiting drugs is prepared; 2) a model for inhibiting pancreatic cancer metastasis is prepared; and a nucleotide sequence of the miRNA-203a-3p is as shown in SEQ ID NO:1. It is discovered that the miRNA-203a-3p is incapableof inhibiting pancreatic cancer cell proliferation and tumorigenesis, but can induce negative correlation expression of a pancreatic cancer cell metastasis related gene CERKL, and can be used for preparing the mouse model for inhibiting the pancreatic cancer metastasis; and the model can be applied to screening of the pancreatic carcinoma metastasis inhibiting drugs and is used as a tool for researching a mechanism of development from in-situ tumor (pancreatic cancer) to metastatic tumor (pancreatic cancer).

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of miRNA-203a-3p in the development of drugs for inhibiting pancreatic cancer. Background technique [0002] Pancreatic cancer (PC) is one of the most common cancer types in gastrointestinal tumors, the fourth leading cause of cancer death in the United States, and one of the malignant tumors with the worst prognosis. Only a few patients have a chance of cure. At the time of diagnosis, most PDAC patients are found at advanced stages beyond surgical resection, a statistic that has remained largely unchanged over the past forty years. Patients with pancreatic cancer are characterized by a lack of clinical manifestations until advanced stages, leading to poor prognosis and high mortality. Only about 8% of pancreatic tumors are localizable and amenable to resection. Current pancreatic cancer biomarkers have relatively low sensitivity and specificity, which limits the sc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/027A61K31/7088A61K49/00C12Q1/6886
CPCA01K67/0275A61K49/0008A61K31/7088C12Q1/6886A01K2227/105A01K2267/03A01K2267/0393A01K2217/03A01K2207/05C12Q2600/158C12Q2600/178
Inventor 章广玲张荣花熊亚南刘志勇
Owner NORTH CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY
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