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Application of miRNA‑27b in antitumor drug resistance

A miRNA-27b, tumor technology, applied in the field of biotechnology and medicine, can solve problems such as unclear miRNA personalized treatment

Active Publication Date: 2017-11-10
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These studies laid the foundation for elucidating the relationship between miRNAs and drug resistance, but so far, especially in the study of liver cancer and kidney cancer, no paper has systematically analyzed which of the numerous human miRNAs regulate drug resistance key factor in sex, and it is unclear how to use miRNAs for personalized therapy

Method used

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  • Application of miRNA‑27b in antitumor drug resistance
  • Application of miRNA‑27b in antitumor drug resistance
  • Application of miRNA‑27b in antitumor drug resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0269] Example 1 Screening of miRNAs capable of enhancing drug sensitivity

[0270] Methods: High-throughput screening was used to search for miRNAs that enhance drug sensitivity. The screening library contained 828 synthetic human miRNA mimics.

[0271] Plate 1x10 in a 96-well plate 4 A liver cancer cell line, HepG2 cells (purchased from ATCC), was transfected with miRNA mimics into the cells 24 hours later with the transfection reagent Lipofectamine RNAiMAX (Invitrogen). Two wells were transfected with each miRNA. One of the wells was cultured with 0.1 μM doxorubicin 48 hours after the transformation, and the other well was left untreated. After 3 days, the number of viable cells was measured with CellTiter-Glo Luminescent Cell Viability Assay (Promega).

[0272] The cell viability determined by each miRNA was defined as: the number of cells treated with doxorubicin / the number of untreated cells.

[0273] Normalized cell viability was defined as: cell viability determin...

Embodiment 2

[0280] Example 2 screens the miRNAs that enhance drug sensitivity obtained in Example 1, and obtains key miRNAs

[0281] Method: Use Targetscan to predict the target gene of each miRNA, such as figure 1 As shown in d, and then use the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the signaling pathways that each miRNA may target. Finally, use Cytoscape software to map miRNAs and their targeted signaling pathways, as shown in figure 1 shown in e.

[0282] Results: Among them, 11 miRNAs can coordinately regulate some common signaling pathways, which are closely related to cell proliferation, apoptosis and metabolism.

[0283] Among them, miR-27b connects the largest number of pathways and is located at the core of the "miRNA-signaling pathway" regulatory network. Therefore, the experiment infers that miR-27b may enhance tumor cell drug resistance by regulating a variety of downstream key signaling pathways. sensitivity.

Embodiment 3

[0284] Example 3 miR-27b can reduce the IC50 of chemotherapeutics

[0285] Plate 1x10 in a 96-well plate 4 1 HepG2 cells, miRNA mimics (final concentration 50nM) were transfected into cells with transfection reagent Lipofectamine RNAiMAX (Invitrogen) after 12 hours. After 48 hours of transfection, culture medium containing different concentrations of doxorubicin was replaced for culture. After 3 days, the number of viable cells was measured with CellTiter-Glo Luminescent Cell Viability Assay (Promega).

[0286] To analyze the sensitizing effect of miR-27b more carefully, a dose-effect curve of doxorubicin was drawn. Overexpression of miR-27b significantly enhanced the sensitivity of HepG2 cells to doxorubicin, and the IC50 decreased from 0.3 μM to 0.046 μM, reaching a 6.5-fold decrease ( figure 2 a). Furthermore, reducing the expression of endogenous miR-27b using a miR-27b inhibitor caused IC 50 Value increased by 1.7 times ( figure 2 b).

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Abstract

The present invention relates to the application of miRNA-27b in anti-tumor drug resistance. Specifically, the present invention studies tumor tissues of tumor patients and conducts large-scale screening of human miRNA libraries through high-throughput microRNA chips. Among a large number of microRNAs, it is found that miR-27b is generally down-regulated in tumors, and miR-27b family members It can improve the sensitivity of tumor cells to anti-tumor drugs. The present invention also finds that miR-27b targets genes such as p53 and CYP1B1 in the tumor drug resistance signaling pathway; promoting p53 and inhibiting CYP1B1 expression can improve the sensitivity of tumors to anti-tumor drugs.

Description

technical field [0001] The invention belongs to the fields of biotechnology and medicine, in particular, the invention relates to microRNAs related to anti-tumor drug resistance and applications thereof. Background technique [0002] The use of antitumor drugs is an important option for tumor treatment, especially for advanced tumors that cannot be surgically removed. However, clinical studies have shown that the resistance of tumor cells to drugs is the main reason for drug failure, especially for two types of solid tumors, liver cancer and kidney cancer, where drug resistance is particularly serious. Sorafenib is one of the most effective target-specific drugs. One, it can only temporarily prolong the patient's survival time by three months. Moreover, once tumor cells develop resistance to a certain drug, they often develop resistance to other structurally and functionally irrelevant drugs. This phenomenon of multidrug resistance suggests that tumor cells may adopt some ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61P35/00C12Q1/68C12N15/11
Inventor 惠利健慕文婧胡超博
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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