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Long non-coding RNA BDNF-AS and application thereof as marker and therapeutic target

A RNABDNF-AS, non-coding technology, applied in the field of long non-coding RNABDNF-AS and its application as a marker and therapeutic target, can solve problems such as overtreatment, lack of drug selection, and reduced patient compliance, and avoid Blind treatment, improve treatment effect, avoid the effect of over treatment

Inactive Publication Date: 2021-08-03
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Endocrine therapy is a common method for treating this type of breast cancer in the prior art. Although it is a more effective treatment method in the prior art, it still has relatively large defects, namely, primary or secondary endocrine resistance in endocrine therapy. This type of drug resistance will seriously affect the treatment effect of patients, making the treatment effect unable to meet expectations
[0003] Although existing technologies have developed mTOR inhibitors, PI3K inhibitors, and CDK4 / 6 inhibitors and other drugs based on primary or secondary endocrine resistance mechanisms and applied them clinically, in general, a small number of tumor-targeted drugs It is still far from meeting the needs of clinical treatment, and there are gaps in drug selection
At the same time, there is a certain blindness in the current clinical tumor treatment, which can only classify tumors by staging and grading or use limited molecular markers to classify tumors, which cannot effectively identify tumors with good prognosis and poor prognosis. Tumors may be over-treated, resulting in poor treatment effects and reduced patient compliance; moreover, the existing technology cannot effectively judge the sensitivity of tumors to drugs, and the formulation of treatment plans has a certain degree of blindness

Method used

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  • Long non-coding RNA BDNF-AS and application thereof as marker and therapeutic target
  • Long non-coding RNA BDNF-AS and application thereof as marker and therapeutic target
  • Long non-coding RNA BDNF-AS and application thereof as marker and therapeutic target

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] qPCR detection of the expression of long non-coding RNA BDNF-AS

[0036] (1) Primer design: The sequence of the long non-coding RNA BDNF-AS was found from the gene library NCBI, and primers were designed with Primer software.

[0037] Forward: 5'-TCACATCTTAGCCCCTTAGCC-3' (SEQ ID NO:4)

[0038] Reverse: 5'-TTTAGCACCCAACAGAATCCC-3' (SEQ ID NO:5)

[0039] (2) qPCR detection (using conventional experimental conditions and steps):

[0040] The expression levels of long non-coding RNA BDNF-AS in breast cancer endocrine-sensitive cell lines and breast cancer endocrine-resistant cell lines were detected. Such as figure 1 As shown, MCF-7 and T47D are tamoxifen-sensitive breast cancer cell lines; MCF-7R and T47DR are tamoxifen-resistant breast cancer cell lines; The expression in the cell lines was significantly higher than that in the breast cancer endocrine-sensitive cell lines. BDNF-AS is specific, that is, based on the expression level of BDNF-AS, it can detect whether t...

Embodiment 2

[0042] In situ hybridization was used to detect the expression of long non-coding RNA BDNF-AS in endocrine-sensitive breast cancer and endocrine-resistant breast cancer.

[0043] Steps include:

[0044] S1. Prepare a tissue chip from the paraffin-embedded breast tissue, perform routine paraffin sectioning, dewax with xylene, and hydrate with gradient alcohol;

[0045] S2. Apply 0.05% trypsin to the section obtained in S1 at room temperature for 10 minutes to enzymatically digest the protein, then add 4% paraformaldehyde and maintain it for 20 minutes for fixation, and finally wash with PBS;

[0046]S3. Treat the slices in the pre-hybridization solution for 2 hours, discard the pre-hybridization solution, and incubate overnight at 52°C with 20nM probes; wash 2 times with 2×SSC for 5 minutes each time, and then wash with 50% formamide Wash 3 times with 2×SSC, 25min each time, and finally wash 5 times with PBST, 5min each time;

[0047] S4. Block with 10% normal goat serum at r...

Embodiment 3

[0051] In situ hybridization detection combined with clinicopathological data to analyze the relationship between long non-coding RNA BDNF-AS and tumor prognosis in breast cancer and the diagnostic efficacy of endocrine drug resistance in breast cancer.

[0052] Specifically, the result is as image 3 shown, where image 3 The left figure shows the efficacy of BDNF-AS in diagnosing endocrine drug-resistant breast cancer, and the right figure shows the correlation analysis between BDNF-AS and the overall survival rate of breast cancer (P value has statistical significance).

[0053] From image 3 (Right) It can be seen that in breast cancer, compared with the low expression group of long non-coding RNA BDNF-AS, the prognosis of the high expression group is significantly worse, and the survival rate of the high expression group is lower than that when the number of days is gradually increased. Fast, and the survival rate was significantly lower than that of the low expression ...

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Abstract

The invention relates to a long non-coding RNA BDNF-AS and application thereof in preparing a product for diagnosing tumors or judging prognosis conditions of breast cancer treatment or judging drug resistance of breast cancer endocrine treatment or treating tumors. The BDNF-AS is taken as a marker, whether breast cancer cells in a sample are resistant to drugs and the prognosis condition of breast cancer can be judged by detecting the expression level of the BDNF-AS in the sample, so that a more effective treatment method is implemented based on a judgment result, the treatment effect is improved, and more side effects caused by blind dosage are avoided. Meanwhile, the long non-coding RNA BDNF-AS can also be used as a treatment target, and the sensitivity of endocrine treatment of the drug-resistant breast cancer to an endocrine treatment drug can be improved by knocking down the BDNF-AS, so that the treatment effect of the drug is improved; the tumor growth can be directly inhibited by singly knocking down the BDNF-AS, so that the BDNF-AS can be combined with other endocrine treatment medicines to realize a synergistic treatment effect.

Description

technical field [0001] The present invention relates to the field of genetic engineering, more specifically, relates to a long non-coding RNA BDNF-AS and its application as a marker and therapeutic target. Background technique [0002] Breast cancer is the female malignant tumor with the highest incidence rate in the world today, with an annual incidence of about 304,000. The incidence rate continues to rise, seriously affecting women's health. Nearly 70% of breast cancers are hormone receptor-positive breast cancers, so the treatment methods and drugs based on hormone receptor-positive breast cancer are very important. Endocrine therapy is a common method for treating this type of breast cancer in the prior art. Although it is a more effective treatment method in the prior art, it still has relatively large defects, that is, primary or secondary endocrine resistance in endocrine therapy. Such drug resistance characteristics will seriously affect the treatment effect of pat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113C12Q1/6886A61K31/138A61K31/7088A61P35/00
CPCC12N15/113C12Q1/6886A61K31/138A61K31/7088A61P35/00C12N2310/11C12Q2600/158C12Q2600/178C12Q2600/118C12Q2600/106A61K2300/00
Inventor 林晓榕姚和瑞胡海丁林潇潇
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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