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Oligonucleotides targeting snhg17 to treat breast cancer

An oligonucleotide and antisense oligonucleotide technology, applied in the field of oligonucleotides targeting SNHG17 in the treatment of breast cancer, can solve the problems of metastasis and recurrence, treatment failure, and no effective target drugs

Active Publication Date: 2020-04-21
SHENZHEN PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, triple negative breast cancer (TNBC) is the most malignant type of breast cancer, because the surface of TNBC cells does not express estrogen receptor (Estrogen receptor, ER), progesterone receptor (Progesterone receptor) , PR) and human epidermal growth factor receptor-2 (Human epidermal growth factor receptor-2, HER-2), leading to the application of no effective target drug so far, so that TNBC patients have a poor prognosis
Within 2 years after the diagnosis of TNBC patients, local invasion, vascular infiltration and extravasation, and distant survival and colonization will lead to metastasis and recurrence. The re-application of chemotherapy drugs will cause the patient's tumor cells to develop drug resistance, resulting in treatment failure.

Method used

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  • Oligonucleotides targeting snhg17 to treat breast cancer
  • Oligonucleotides targeting snhg17 to treat breast cancer
  • Oligonucleotides targeting snhg17 to treat breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] This example relates to the influence of SNHG17RNA expression level in tumor tissues of patients with triple negative breast cancer (TNBC):

[0077] Collect the cancer tissues (Cancer), adjacent tissues (Peritumorial) and sentinel node tissues (Sentinel node) of 3 groups of clinical TNBC patients, extract RNA respectively, and perform qRT-PCR detection after reverse transcription. The results are as follows figure 1 Shown ( figure 1 Medium, *p <0.05, **p <0.01, ***p <0.001), the expression of SNHG17RNA in TNBC tumor tissue is much higher than the expression of SNHG17RNA in adjacent tissues and sentinel lymph node tissues.

[0078] Conclusion: SNHG17 gene is related to the occurrence of TNBC.

Embodiment 2

[0080] This example relates to the detection of the ability of antisense oligonucleotides to regulate the proliferation of MDA-MB-231 and BT549 cells and the expression level of SNHG17 RNA in tumor tissues of TNBC patients.

[0081] In TNBC cell lines MDA-MB-231 and BT549, NC ASO and SNHG17 ASO interference models were established by the above experimental methods.

[0082] The qRT-PCR method was used to detect the changes in the expression level of SNHG17RNA in the MDA-MB-231 cells transfected with NC ASO and SNHG17 ASO, specifically as follows figure 2 As shown, the SNHG17RNA expression level of MDA-MB-231 cells transfected with SNHG17 ASO was much lower than that of the control group (NC ASO), and the SNHG17 ASO interference model was successfully established; image 3 Indicates the changes in the proliferation of MDA-MB-231 cells after NCASO and SNHG17 ASO were treated 0h, 24h, 48h and 72h after interference with SNHG17 ( image 3 Medium, *p image 3 It can be seen that after tr...

Embodiment 3

[0086] This example relates to detecting the effect of antisense oligonucleotides on the migration and invasion of MDA-MB-231 and BT549 cells in tumor tissues of TNBC patients.

[0087] In this example, Transwell technology was used to detect the migration and invasion ability of MDA-MB-231 and BT549 cells in the SNHG17 ASO interference model. The specific steps are as follows:

[0088] Transfect NC ASO and SNHG17 ASO into MDA-MB-231 cells. After 48 hours of transfection, transfect the treated MDA-MB-231 into a Transwell chamber (the chamber for detecting the invasion ability contains Matrigel), 12- Collect cells at 16h for observation under a microscope, please refer to Image 6 , Figure 7 versus Figure 8 , Image 6 Electron micrographs of cell migration and invasion of MDA-MB-231 cells 48h after NC ASO and SNHG17 ASO transfection, Figure 7 After transfecting MDA-MB-231 cells with NC ASO and SNHG17 ASO for 48h, Image 6 Cell migration electron microscope image of cell number sta...

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Abstract

The invention provides an oligonucleotide targeting SNHG17 for treating breast cancer. The oligonucleotide comprises at least one of an antisense oligonucleotide and small interfering RNA, wherein thesequence of the antisense oligonucleotide is as shown in SEQ ID NO.1, and the sequence of the small interfering RNA is as shown in SEQ ID NO.2-4. The oligonucleotide can regulate and control the proliferation, metastasis and invasion capability of triple-negative breast cancer cells by targeting and silencing SNHG17 gene or down-regulating the expression of the SNHG17 gene in the triple-negativebreast cancer cells, and finally improve or treat triple-negative breast cancer.

Description

Technical field [0001] The invention relates to the technical field of gene therapy, in particular to an oligonucleotide targeting SNHG17 to treat breast cancer. Background technique [0002] Breast cancer is one of the most common female cancers. In China, the average age of breast cancer is 45-55 years, earlier than Western women. Newly diagnosed breast cancer cases accounted for 12.2% of all cancers; as of 2008, breast cancer was the first death of Chinese women from cancer. Six causes of death are ranked after lung cancer, stomach cancer, liver cancer, esophageal cancer and colorectal cancer. The age-standardized ratio (ASR) is 5.7 per 100,000 women, accounting for 9.6% of the global breast cancer deaths. At the same time, due to multiple The reason is that many new drugs are not available to limit the progress of systemic treatment of breast cancer; at the same time, neoadjuvant chemotherapy is more common. About 81.4% of patients with invasive breast cancer will undergo ch...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/113A61K31/7105A61P35/00
CPCA61K31/7105A61P35/00C12N15/1135C12N2310/141
Inventor 高琳邱俊莹洪马林邹畅周文斌
Owner SHENZHEN PEOPLES HOSPITAL