Application of yy1 expression inhibitor in preparation of medicament for breast cancer

An inhibitor and breast cancer technology, applied in the field of gene therapy, can solve problems such as unclear molecular biological mechanisms

Active Publication Date: 2020-06-26
SHENZHEN PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, many studies on YY1 in tumors are still in the preliminary stage
For example, there is no report on how the YY1 / KTN1 signaling pathway regulation axis works in triple-negative breast cancer; at the same time, its underlying molecular biological mechanism is still unclear

Method used

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  • Application of yy1 expression inhibitor in preparation of medicament for breast cancer
  • Application of yy1 expression inhibitor in preparation of medicament for breast cancer
  • Application of yy1 expression inhibitor in preparation of medicament for breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] This embodiment relates to the RNA expression of YY1 gene in the tumor tissue of patients with triple negative breast cancer (TNBC):

[0109] First, the expression of the YY1 gene in the Cancer Genome Atlas (TCGA) database was analyzed, and the results were as follows: figure 1 shown; figure 1 Shows the RNA expression situation of YY1 gene in breast cancer tissue and paracancerous tissue in Cancer Genome Atlas Project (TCGA) database; figure 1 It can be seen that the RNA expression level of YY1 gene in 1085 cases of invasive breast cancer tumors (BRCA) is much higher than that of adjacent tissues (291 cases), and YY1 RNA is highly expressed in invasive breast cancer tumors (BRCA).

[0110] In addition, tumor tissues and paracancerous tissues of 4 groups of clinical patients with TNBC were collected for qRT-PCR detection, and the results were as follows: figure 2 as shown ( figure 2 Among them, *p figure 2 Indicates the expression of YY1RNA in tumor tissues and para...

Embodiment 2

[0113] This example involves detecting the effect of KTN1 gene on the proliferation of TNBC cell lines MDA-MB-231 and BT549 cells and the expression of KTN1 RNA.

[0114] KTN1 gene silencing model construction: when the confluence of MDA-MB-231 and BT549 cells reached 70%, the MDA-MB-231 and BT549 cells were divided into three groups, namely siNC' group, siKTN1_1 group and siKTN1_2 group.

[0115] 30 μl lipofectamine2000 liposomes were used to mix 50 nM 15 μL siNC', siKTN1_1 and siKTN1_2, respectively, and then diluted with serum-free and antibiotic-free DMEM medium to obtain three groups of mixed solutions. The total volume of each diluted mixed solution was 400 μl. Wherein, the sequence of siKTN1_1 is: 5'-GAGTGATCTTTCTAGCAAA-3', as shown in SEQ ID NO.1; the sequence of siKTN1_2 is: 5'-GAAGTCTGGTGTAATACAA-3', as shown in SEQ ID NO.2; the siNC' group is a negative control Group, siNC' is provided by Guangzhou Ruibo Biotechnology Co., Ltd., its product name is siR NC#1, and its...

Embodiment 3

[0122] This example involves detecting the effect of knocking down the YY1 gene on the transcription and translation of KTN1.

[0123] First, the correlation between the expression of YY1RNA and the expression of KTN1RNA in invasive breast cancer tumors and adjacent tumors was queried through the TCGA database, Figure 6 Indicates the correlation between YY1RNA expression and KTN1RNA expression in invasive breast cancer tumors and adjacent tumors (correlation coefficient R>0.5, P Figure 6 It can be seen that in invasive breast cancer tumors and adjacent tumors, there is a significant positive correlation between the expression of YY1RNA and the expression of KTN1RNA (correlation coefficient R>0.5, P<0.001), and it is speculated that there is a regulatory function between YY1 gene and KTN1RNA expression.

[0124] Since the expression of genes needs to be regulated by transcription factor proteins, and transcription factors are a kind of specific sequences that can specifically b...

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Abstract

The invention provides application of a YY1 expression inhibitor in the preparation of drugs to treat breast cancer. Research results herein show that in triple-negative breast cancer YY1 protein canbond to KTN1 promoter region to regulate KTN1 gene expression, and that KTN1 gene expression is positively correlated with triple-negative breast cancer, while targeted silencing of YY1 helps evidently inhibit KTN1 expression, so that triple-negative breast cancer is improved or treated. SiRNA disclosed herein can silence YY1 in targeted manner to treat triple-negative breast cancer; sequences ofsiRNA include at least one of a sequence shown as SEQ ID NO. 1 and a sequence shown as SEQ ID NO. 2. A reagent disclosed herein is suitable for monitoring and detecting triple-negative breast cancer and has good practical application value.

Description

technical field [0001] The invention relates to the field of gene therapy, in particular to the application of a YY1 expression inhibitor in the preparation of drugs for treating breast cancer. Background technique [0002] Breast cancer is a malignant tumor that occurs in the breast epithelium. As of 2012, breast cancer has become the most common cancer in women worldwide, and about 520,000 people died of breast cancer worldwide. In China, breast cancer accounts for approximately 15% of newly diagnosed cancers in women. It is estimated that by 2035, about 2.5 million Chinese women will be diagnosed with new breast cancer patients, which will seriously threaten women's health and cannot be ignored. According to different molecular types, breast cancer can be divided into estrogen / progesterone receptor (ER / PR) positive breast cancer, Her-2 receptor positive breast cancer and triple negative breast cancer (TNBC for short). . Although TNBC only accounts for 15%-20% of breas...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K48/00A61K31/713A61P35/00C12Q1/6886C12N15/11
CPCA61K31/713A61K45/00A61P35/00C12Q1/6886C12Q2600/118C12Q2600/158
Inventor 高琳邱俊莹洪马林彭政邹畅
Owner SHENZHEN PEOPLES HOSPITAL
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