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Application of micropeptide ASRPS in treating cancer

A micropeptide, cancer technology, applied in the field of biomedicine, to achieve the effect of inhibiting the formation of breast cancer blood vessels

Active Publication Date: 2019-09-10
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previously, people defined long non-coding RNAs as transcripts that do not encode proteins, but recent studies have shown that there are many short open reading frames on long non-coding RNAs, which may encode some micropeptides, and these micropeptides may have some physiological functions

Method used

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  • Application of micropeptide ASRPS in treating cancer
  • Application of micropeptide ASRPS in treating cancer
  • Application of micropeptide ASRPS in treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 ASRPS gene knockout promotes TNBC tumor growth

[0061] See Figure 1A to Figure 1D , experimentally determined the effect of ASRPS knockout on tumor growth using a mouse TNBC xenograft model.

[0062] The inventors used a mouse TNBC xenograft model to study the effect of ASRPS gene knockout on tumor growth. The tumor volume line graph showed that the tumor growth of ASRPS knockout TNBC cells was significantly higher than that of wild-type TNBC cells ( Figure 1A ). To investigate the role of LINC00908 transcripts in TNBC tumor growth, we knocked out LINC00908 in wild-type and ASRPS knockout TNBC cells. We found that knockout of LINC00908 promoted the growth of wild-type TNBC cells but not ASRPS knockout TNBC cells ( Figure 1B and Figure 1C ).

[0063] Furthermore, we found that reintroduction of full-length LINC00908 or ASRPS in ASRPS knockout reversed tumor growth ( Figure 1D ). The results showed that ASRPS could significantly promote the growth o...

Embodiment 2

[0064] Example 2 Micropeptide ASRPS inhibits tumor angiogenesis

[0065] See Figure 2A to Figure 2D , the micropeptide ASRPS inhibits tumor angiogenesis.

[0066] The inventors cultured human umbilical vein endothelial cells (HUVEC) in conditioned medium prepared from MDA-MB-231 cells and Hs578T cells, and treated them with ASRPS overexpression and knockout. Using 3D spheroid-based in vitro angiogenesis assays, overexpressed ASRPS caused HUVECs to produce shorter shoots than controls, and knockdown of ASRPS strongly promoted shoot growth compared with WT ( Figure 2A ). Next, we performed the Matrigel plug angiogenesis assay in vivo. When Matrigel was mixed with ASRPS overexpression cell culture medium, the Matrigel plug was light white, while the ASRPS removal group was bright red, HE results showed that the more ASRPS, the more blood vessels ( Figure 2B ). Next, the inventors used a mouse xenograft model to determine the effect of ASRPS overexpression and gene knockou...

Embodiment 3

[0067] Example 3 Micropeptide ASRPS inhibits angiogenesis of breast cancer in MMTV-PyMT mice

[0068] See Figure 3A to Figure 3B , Effect of micropeptide ASRPS on angiogenesis of breast cancer in MMTV-PyMT mice.

[0069] To gain insight into the effect of ASRPS on breast cancer angiogenesis, the inventors applied ASRPS to 186B / 6 mice crossed with MMTV-PyMT mice to generate MMTV-PyMT;ASRPS+ / + mice. Anti-CD31 immunohistochemical staining showed that tumor vessel recruitment in MMTV-PyMT and ASRPS+ / + mice decreased ( Figure 3A ). Furthermore, to investigate the effect of exogenous ASRPS treatment on angiogenesis, we injected ASRPS into the mammary pads of MMTV-PyMT mice and demonstrated that ASRPS can significantly inhibit primary tumor angiogenesis ( Figure 3B ). In conclusion, the micropeptide ASRPS has an important anti-angiogenic effect in the MMTV-PyMT mouse model.

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Abstract

The invention relates to application of micropeptide ASRPS in treating cancer. From the perspective of the translation level of the micropeptide encoded by lncRNA, the influence of the micropeptide onangiogenesis of triple negative breast cancer is studied, and the important role of the micropeptide in triple negative breast cancer is demonstrated. The micropeptide ASRPS affects angiogenesis of triple negative breast cancer, and the signal transduction and the activation of an activating transcription factor 3 (STAT3) are thus influenced by changing the expression amount of the micropeptide,so that the expression of a vascular endothelial growth factor (VEGF) is influenced, and the angiogenesis capability of triple negative breast cancer is influenced. It is proved by in-vivo and in-vitro experiments that the micropeptide ASRPS obviously inhibits angiogenesis of breast cancer through a STAT3-VEGF pathway, and the micropeptide ASRPS has a clinical medicinal value for treating triple negative breast cancer.

Description

technical field [0001] The invention relates to the application of a micropeptide ASRPS in the treatment of cancer, which belongs to the field of biomedicine. Background technique [0002] Breast cancer is one of the most common malignant tumors in women. Worldwide, breast cancer accounts for 10% of all cancers, 25-30% of malignant tumors in women, and 15% of cancer-related mortality in women. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that accounts for 15% of all breast cancers. TNBC is negative for estrogen receptor (ER) and progesterone receptor (PR) expression and lacks HER2 amplification or overexpression. Compared with other breast cancers, triple-negative breast cancer has the characteristics of younger onset, high degree of malignancy, easy recurrence and metastasis, and low survival rate. In addition, triple-negative breast cancer lacks targets for endocrine therapy and targeted therapy, so triple-negative breast cancer Breast cancer has b...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61P35/00
CPCA61K38/16A61P35/00
Inventor 周翊峰邓杰琼王艺蓉张征吴思奇
Owner SUZHOU UNIV
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