CN-121987656-A - Use of CIRCVEGFC in the treatment of rhabdomyosarcoma

Abstract

The invention belongs to the field of biological medicines, relates to an application of CIRCVEGFC in rhabdomyosarcoma treatment, and in particular relates to an application of CIRCVEGFC in preparation of a medicament for treating rhabdomyosarcoma, wherein the sequence of CIRCVEGFC is SEQ ID NO. 1. The invention remarkably inhibits the proliferation and migration of rhabdomyosarcoma cells by promoting CIRCVEGFC expression and promotes rhabdomyosarcoma differentiation. Furthermore CIRCVEGFC in combination with mTOR pathway inhibitors, such as rapamycin, can synergistically inhibit tumor proliferation.

Inventors

• NI XIN
• YANG LEI
• JIN YAQIONG
• ZHANG CONG
• CUI JIALIN
• XIE XINXIN

Assignees

• 首都医科大学附属北京儿童医院

Dates

Publication Date

20260508

Application Date

20260318

Claims (9)

1. Use of circvegfc for the manufacture of a medicament for the treatment of rhabdomyosarcoma, characterized in that the sequence of CIRCVEGFC is SEQ ID No. 1.
2. 2. The use according to claim 1, wherein the medicament comprises an agent that promotes CIRCVEGFC expression.
3. 3. The use according to claim 2, wherein the agent that promotes CIRCVEGFC expression is a CIRCVEGFC over-expression construct.
4. 4. The use according to claim 3, wherein the vector of CIRCVEGFC over-expression construct is an adenovirus vector, an adeno-associated virus vector, a lentiviral vector, a retroviral vector or an exosome vector.
5. 5. The use according to claim 1, wherein the rhabdomyosarcoma is an embryonic or acinar rhabdomyosarcoma.
6. 6. The use according to any one of claims 1-5, wherein the medicament further comprises a second medicament.
7. 7. The use of claim 6, wherein the second agent is an mTOR pathway inhibitor.
8. 8. The use according to claim 7, wherein the mTOR pathway inhibitor is a rapamycin.
9. 9. The use according to claim 8, wherein the rapamycin is everolimus.

Description

Use of CIRCVEGFC in the treatment of rhabdomyosarcoma Technical Field The invention belongs to the field of biological medicines, relates to an application of CIRCVEGFC in rhabdomyosarcoma treatment, and in particular relates to an application of CIRCVEGFC in preparation of a medicament for treating rhabdomyosarcoma. Background Rhabdomyosarcoma (Rhabdomyosarcoma, RMS) is one of the most common types of soft tissue sarcomas in children and adolescents, originating from mesenchymal cells with skeletal muscle differentiation potential. Despite the low overall incidence, accounting for only about 1% of all malignant tumors, RMS is highly biologically heterogeneous and invasive. RMS is largely classified into embryonic, acinar, fusiform and polymorphic forms according to molecular and histological characteristics. Gene therapy has been developed rapidly in recent years as an innovative treatment strategy for diseases related to genetic factors (including malignant tumors, congenital genetic diseases, etc.). The core idea is to deliver exogenous nucleic acid substances (DNA/RNA) to target cells to achieve therapeutic goals by correcting abnormal gene expression or restoring physiological function. The gene therapy approach to tumors usually utilizes viral or non-viral vectors to precisely introduce tumor suppressor genes, immune regulatory factors or gene editing systems into tumor cells to induce tumor suppression, immune activation or apoptosis. Currently, various gene therapy products have been developed in clinical or transformation studies. For example, oncolytic virus-based gene therapy has been of interest in the treatment of solid tumors, and a class of recombinant viruses can selectively infect and lyse tumor cells while stimulating host anti-tumor immune responses, providing a new therapeutic option for resistant or recurrent tumors. Along with the continuous maturation of delivery systems and gene editing technologies, gene therapy is gradually going from theory to clinic, bringing a brand new therapeutic mode for refractory tumors. Of interest, circular RNAs (circrnas) exhibit high stability due to their covalently closed structure, and have cell type and tissue specific expression characteristics, making them hot spots in functional research and disease marker discovery in recent years. A large number of researches show that the circRNA is taken as an important non-coding RNA, and can participate in gene expression regulation and control through mechanisms such as sponging microRNA, regulating RNA binding protein, influencing transcription and translation processes and the like, and is closely related to biological processes such as tumorigenesis, development, immunoregulation, cell stress response and the like. The lack of a 5 'and 3' end of its closed loop structure renders it naturally resistant to exonucleases, thereby maintaining a longer half-life in the cellular environment. Recent literature further indicates that dysfunction of circRNA in the nervous system, cardiovascular system and various malignancies may be associated with driving events or drug resistance development of the disease. Thus, circRNA is not only a potential biomarker, but also provides a new target and direction for nucleic acid drug and RNA therapeutic strategies. Disclosure of Invention The invention provides an application of CIRCVEGFC in preparing a medicament for treating rhabdomyosarcoma, which is characterized in that the sequence of CIRCVEGFC is SEQ ID NO. 1. Preferably, the medicament comprises an agent that promotes CIRCVEGFC expression. More preferably, the agent that promotes CIRCVEGFC expression is a CIRCVEGFC over-expression construct. More preferably, the vector of the CIRCVEGFC over-expression construct is an adenovirus vector, an adeno-associated virus vector, a lentiviral vector, a retroviral vector, or an exosome vector. Preferably, the rhabdomyosarcoma is an embryonic type rhabdomyosarcoma or an acinar type rhabdomyosarcoma. Preferably, the medicament further comprises a second medicament. More preferably, the second agent is an mTOR pathway inhibitor. More preferably, the mTOR pathway inhibitor is a rapamycin. More preferably, the rapamycin is everolimus. Compared with normal cells, the invention discovers that CIRCVEGFC is down-regulated in the rhabdomyosarcoma cells, the expression quantity of CIRCVEGFC in the tissue of a rhabdomyosarcoma patient is obviously lower than that of normal muscle tissue, the over-expression CIRCVEGFC can obviously inhibit the proliferation of the rhabdomyosarcoma cells and promote the tumor differentiation, and the knock-down CIRCVEGFC can enhance the proliferation of the rhabdomyosarcoma cells and inhibit the tumor differentiation. The result shows that CIRCVEGFC plays an important role in the generation and development processes of rhabdomyosarcoma, shows good application prospects of gene therapy, and provides a new idea for the accurate treatment, targeted treatment, d