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Novel exosome release related target and application thereof to monitoring and inhibiting of tumors

An exosome and tumor technology, applied in the field of biomedicine, can solve the problems of accelerating the progress of aging-related diseases such as tumors, and changing the structure and function of the surrounding microenvironment.

Active Publication Date: 2021-03-19
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the effectors released by SASP-secreting cells can stimulate the immune response of local tissues in the body and promote the clearance of senescent cells, they can significantly change the structure and function of the surrounding microenvironment and accelerate the progression of aging-related diseases such as tumors.

Method used

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  • Novel exosome release related target and application thereof to monitoring and inhibiting of tumors
  • Novel exosome release related target and application thereof to monitoring and inhibiting of tumors
  • Novel exosome release related target and application thereof to monitoring and inhibiting of tumors

Examples

Experimental program
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Effect test

Embodiment 1

[0167] Example 1. Aging cells can release a large number of exosomes and exhibit abnormal particle size distribution and other characteristics

[0168] Previous reports on exosomes in cancer research mostly focused on the study of cancer cells themselves or proliferating cells. In contrast, changes in senescent cells in patient stromal tissues have been rarely reported. At present, the inventors have noticed that the human prostate stromal cell line PSC27 (mainly composed of fibroblasts) will rapidly enter a senescent state after being treated with cytotoxic, especially genotoxic chemotherapy drug bleomycin (BLEO) ( Figure 1 ~ Figure 2 ). At the same time, the cells present a typical senescence-associated secretory phenotype (SASP), which is concentrated in the highly up-regulated expression of a large number of exocrine factors ( image 3 ).

[0169] Interestingly, with the development of cell senescence and SASP, the number of extracellular vesicles (extracellular vesicl...

Embodiment 2

[0172] Example 2, Senescent cell exosomes carry small RNA molecules whose components are very different from those of proliferating cells

[0173] In the in vivo environment, extracellular vesicles can transport a variety of biologically active substances, including various types of small RNA molecules, especially microRNAs (miRNAs), which can reflect the pathophysiological characteristics of mother cells and participate in life such as intercellular communication. During the event. To this end, the inventors first performed deep sequencing analysis of microRNAs molecules in stromal cell-derived exosomes by small RNA sequencing (small RNA sequencing, sRNA-Seq). High-throughput data show that the total amount of small RNAs does not show a large difference between proliferating cells and senescent cells, but there are certain changes in specific small RNA subtypes, such as rRNA, tRNA and human gene intron regions Transcripts generated at some points of segment encoding ( Figu...

Embodiment 3

[0176] Example 3. Downregulation of SIRT1 leads to more active biosynthesis of exosomes in senescent cells and a large amount of exosomes released into the extracellular space

[0177] The inventor then thought about a key question: what is the biological basis that causes the significant changes in the molecular components? In recent years, it has been reported that the abnormality of lysosome or autophagy activity can lead to the disorder of exosome biosynthesis process, which is mainly caused by the change of multivesicular bodies (multivesicular bodies, MVBs). main source of body. In particular, the downregulation of SIRT1 expression in some cancer cells can seriously affect the maintenance of lysosomal acidity, and eventually promote the excessive or abnormal release of exosomes.

[0178] In view of this, the present inventors next analyzed SIRT1, a NAD + Dependent sirtuin expression in proliferating and senescent cells. Whole-transcriptome sequencing (RNA-Seq) results...

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Abstract

The invention provides a novel exosome release related target and application thereof to monitoring and inhibiting of tumors. The invention discloses exosomes produced by senescent cells and some biomolecules involved in regulating the exosomes, and the exosomes and the some biomolecules are closely related to drug resistance and tumor prognosis after tumor chemotherapy treatment. Therefore, the invention provides a new target for inhibiting tumors and reversing tumor drug resistance, and a new marker for tumor diagnosis and prognosis evaluation.

Description

technical field [0001] The present invention belongs to the field of biomedicine, and more specifically, the present invention relates to a novel exosome release-related target and its application in monitoring and inhibiting tumors. Background technique [0002] Aging-related diseases mainly include malignant tumors and various organ degenerative diseases such as heart failure, osteoporosis, arthritis, Alzheimer's disease, Parkinson's syndrome, etc., which are the direct factors leading to human death. Among them, malignant tumors have surpassed other diseases in recent years and become the number one killer that endangers human health. Cell senescence, which is closely related to human diseases, was first discovered and proposed by American scientist Hayflick in the 1960s. It is a life phenomenon characterized by the inhibition of normal cell proliferation and cell cycle arrest. Since then, a large number of studies have been devoted to exploring the triggers, signaling p...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886A61K45/06A61P35/00
CPCC12Q1/6886A61K45/06A61P35/00C12Q2600/118
Inventor 孙宇韩柳
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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