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Oligonucleotide targeting SNHG17 for treating 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, no effective target drugs, and treatment failure

Active Publication Date: 2019-07-19
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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  • Oligonucleotide targeting SNHG17 for treating breast cancer
  • Oligonucleotide targeting SNHG17 for treating breast cancer
  • Oligonucleotide targeting SNHG17 for treating breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] This embodiment relates to the impact of SNHG17RNA expression level in the tumor tissue of patients with triple negative breast cancer (TNBC):

[0077] The cancer tissue (Cancer), peritumorial tissue (Peritumorial) and sentinel lymph node tissue (Sentinel node) were collected from 3 groups of clinical TNBC patients, RNA was extracted respectively, and qRT-PCR was performed after reverse transcription. The results are as follows: figure 1 as shown ( figure 1 Among them, *p<0.05, **p<0.01, ***p<0.001), the expression of SNHG17RNA in TNBC tumor tissue was much higher than that in paracancerous tissue and sentinel lymph node tissue.

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

Embodiment 2

[0080] This embodiment relates to the detection of antisense oligonucleotides' ability 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] NC ASO and SNHG17 ASO interference models were established in TNBC cell lines MDA-MB-231 and BT549 by the above-mentioned experimental method.

[0082] qRT-PCR method was used to detect the change of SNHG17RNA expression level of MDA-MB-231 cells transfected with NC ASO and SNHG17 ASO, specifically as follows figure 2 As shown, the SNHG17 RNA 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 After 0h, 24h, 48h and 72h of NCASO and SNHG17 ASO treatment of MDA-MB-231 cells, the changes in the proliferation of MDA-MB-231 cells after interference with SNHG17 were detected by the CCK8 method ( image 3 Among,...

Embodiment 3

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

[0087] This example uses Transwell technology to detect the migration and invasion abilities of MDA-MB-231 and BT549 cells in the SNHG17 ASO interference model. The specific steps are:

[0088] NC ASO and SNHG17 ASO were transfected in MDA-MB-231 cells. After 48 hours of transfection, the treated MDA-MB-231 was transplanted in a Transwell chamber (the chamber for detecting invasion ability contained Matrigel), and 12- Collect cells at 16h and observe under a microscope, please refer to Figure 6 , Figure 7 and Figure 8 , Figure 6 Electron micrographs of cell migration and invasion after transfection of NC ASO and SNHG17 ASO in MDA-MB-231 cells for 48 hours, Figure 7 48h after transfecting MDA-MB-231 cells for NC ASO and SNHG17 ASO Figure 6 The cell number statistical diagram of the c...

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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 for treating 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 old, which is earlier than Western women, and newly diagnosed breast cancer cases account for 12.2% of all cancers; as of 2008, breast cancer is the first cause of death from cancer in Chinese women 6 causes of death, after lung cancer, gastric cancer, liver cancer, esophageal cancer and colorectal cancer, the age-standardized ratio (ASR) is 5.7 / 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, which limits the progress of systemic treatment of breast cancer. At the same time, neoadjuvant chemotherapy is relatively common. About 81.4% of patients with invasive bre...

Claims

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Application Information

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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
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