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Application of protein DEPDC1 (Dishevelled and EGL-10, Pleckstrin Domain-Containing protein 1) as marker for diagnosing triple negative breast cancer

A triple-negative breast cancer and marker technology, applied in the field of biomedicine, can solve the problems of poor diagnosis and treatment of triple-negative breast cancer, and achieve the effect of promoting cell proliferation and tumor formation with obvious technical effect.

Active Publication Date: 2019-02-12
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide the use of protein DEPDC1 as a diagnostic marker, and the use of this protein DEPDC1 as a diagnostic marker is to solve the technical problem of poor effect in the diagnosis and treatment of triple-negative breast cancer in the prior art

Method used

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  • Application of protein DEPDC1 (Dishevelled and EGL-10, Pleckstrin Domain-Containing protein 1) as marker for diagnosing triple negative breast cancer
  • Application of protein DEPDC1 (Dishevelled and EGL-10, Pleckstrin Domain-Containing protein 1) as marker for diagnosing triple negative breast cancer
  • Application of protein DEPDC1 (Dishevelled and EGL-10, Pleckstrin Domain-Containing protein 1) as marker for diagnosing triple negative breast cancer

Examples

Experimental program
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Effect test

Embodiment 1

[0045] Example 1 DEPDC1 is upregulated in triple negative breast cancer

[0046] In order to clarify the role of DEPDC1 in triple-negative breast cancer, the present invention analyzed the data of two sets of chips (GSE76250 and GSE81838) on the Gene Expression Omnibus (website: http: / / www.ncbi.nlm.nih.gov / geo), The expression of DEPDC1 in triple-negative breast cancer and paired paracancerous tissues was clarified. as figure 1 As shown in A and 1B, DEPDC1 expression was significantly increased in TNBC tissues compared with paired paracancerous tissues. Similar results can also be obtained in other databases.

[0047] Among the 33 pairs of triple-negative breast cancer and adjacent tissues, the present invention found that the expression of DEPDC1 in most triple-negative breast cancer tissues was higher than that of adjacent tissues (see figure 1 C and 1D). Moreover, the expression of PCNA (nuclear proliferating antigen) and Ki67 (a marker of proliferation, an important in...

Embodiment 2

[0048] Example 2 Overexpression of DEPDC1 in triple-negative breast cancer cells can promote cell proliferation and clone formation.

[0049] Then the present invention detects the mRNA expression of DEPDC1 in a group of triple-negative breast cancer cell lines. In these cells, endogenous DEPDC1 expression was significantly higher in MDA-MB-231 than in other cell lines, whereas DEPDC1 expression was lowest in MDA-MB-436 cells (see figure 2 A). Therefore, a DEPDC1 stable overexpression cell line was constructed in MDA-MB-436 cells.

[0050] Real-time quantitative PCR and western blot were used to detect the mRNA and protein expression levels of DEPDC1 to confirm the transfection efficiency ( figure 2 B and 2C). as image 3 As shown in A, the results of CCK-8 detection showed that the cell viability was significantly increased after the overexpression of DEPDC1. BrdU intercalation assay and PCNA expression were used to detect cell proliferation.

[0051] The present inve...

Embodiment 3

[0054] Example 3 Knocking out DEPDC1 in triple-negative breast cancer can weaken cell proliferation

[0055] In order to determine the physiological function of DEPDC1 in triple negative breast cancer, the present invention also knocked down the expression of DEPDC in MDA-MB-231 cells. The knockout efficiency was also determined by real-time quantitative PCR and western blot ( Figure 4 A and Figure 4 B). like Figure 5 As shown in A, knockdown of DEPDC1 can inhibit the growth of MDA-MB-231 cells. Moreover, both BrdU inhalation and PCNA protein expression levels were attenuated by knocking out DEPDC1 ( Figure 5B and 5C). The results of cell cycle distribution showed that knockdown of DEPDC1 expression increased the proportion of tumor cells in G0 / G1 phase growth arrest (from 56.31% to 78.52%), accompanied by a decrease in S phase cells from 32.41% to 16.31% ( Figure 5 D).

[0056] like Figure 5 As shown in E, knockout DEPDC1 clone formation was inhibited in MDA-MB-...

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Abstract

The invention provides application of protein DEPDC1 (Dishevelled and EGL-10, Pleckstrin Domain-Containing protein 1) as a marker for diagnosing the triple negative breast cancer, and also provides application of miR-26b for preparing a medicine for treating the triple negative breast cancer. The invention also provides application of miR-26b for preparing a medicine for inhibiting DEPDC1 mRNA (Ribonucleic Acid) expression. The invention finds that DEPDC1 expression is obviously higher than a paired para-carcinoma tissue in a triple negative breast cancer tissue. In the triple negative breastcancer cell, overexpression DEPDC1 can accelerate cell growth and tumor formation through FOXM1 (Forkhead box protein M1) expression up-regulation. On the contrary, after the DEPDC1 is knocked down,an inverse function is displayed. In addition, in the triple negative breast cancer, miR-26b serves as a tumor inhibiting factor to directly inhibit DEPDC1 expression and weaken the acceleration function of the DEPDC1 for cell growth and clone formation. The invention points out a new important mechanism for the occurrence, the development, the regulation and the control of the triple negative breast cancer.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a protein, specifically the use of protein DEPDC1 as a diagnostic marker. Background technique [0002] Breast cancer (BC), one of the most prevalent cancers, can be classified into four distinct types based on gene expression profiles: Luminal A subtype, Luminal B subtype, HER2-overexpressing type, and basal-like breast cancer (BLBC). Triple-negative breast cancer (TNBC) is characterized by lack of expression of ER, PR, and HER2 and belongs to basal-like breast cancer. TNBC is highly invasive, with larger tumor volume and tumor burden, and is more likely to metastasize than other subtypes. Currently, the rate of new TNBC diagnoses ranges from 9% to 16%, with a marked increase in younger women. However, TNBC is not sensitive to targeted drugs currently used in clinical practice, and its main treatment method is still chemotherapy. Therefore, finding specific carcinogenic factors is an ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K31/7105A61P35/00
CPCA61K31/7105A61P35/00C12Q1/6886C12Q2600/158G01N33/57415
Inventor 陆劲松张蕾马俊许雅芊徐曙光杨凡
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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