CN-121971478-A - Use of METTL A inhibitor in preparation of product for improving sensitivity of glioma to temozolomide

Abstract

The invention discloses an application of METTL inhibitor in preparing a product for improving sensitivity of glioma to temozolomide, belonging to the field of biological medicine. According to the invention, the nucleotide sequences of si-METTL1-1 shown as SEQ ID NO.1 and si-METTL1-3 shown as SEQ ID NO.2 are used as METTL inhibitors, glioma drug sensitivity research is carried out, and experimental results show that the proliferation, migration and invasion capacities of glioma cells can be effectively reduced and the sensitivity of temozolomide in glioblastoma can be remarkably improved by using METTL1 inhibitors to interfere METTL1 expression. Therefore, METTL inhibitors can be used for diagnosis and treatment of glioma, and can also improve the sensitivity of glioma cells to temozolomide. The invention provides a new auxiliary product for improving the curative effect of the targeted drug and has wide application prospect.

Inventors

• LV QIAOLI
• WANG FEIYU
• CHEN SHUHUI
• JI YULONG
• DENG YUCHEN
• ZHANG JINGWEN

Assignees

• 江西省肿瘤医院(江西省第二人民医院、江西省癌症中心)

Dates

Publication Date

20260505

Application Date

20260402

Claims (8)

1. 1. Use of METTL a inhibitor for the preparation of a product for increasing the sensitivity of glioma to temozolomide.
2. 2. The use of claim 1, wherein the METTL inhibitor is si-METTL1-1 having the nucleotide sequence shown in SEQ ID No.1 or si-METTL1-3 having the nucleotide sequence shown in SEQ ID No. 2.
3. 3. A pharmaceutical composition comprising temozolomide and a METTL inhibitor.
4. 4. The pharmaceutical composition of claim 3, wherein the METTL inhibitor is si-METTL1-1 with a nucleotide sequence shown as SEQ ID No.1 or si-METTL1-3 with a nucleotide sequence shown as SEQ ID No. 2.
5. 5. Use of the pharmaceutical composition of claim 3 or 4 for the preparation of a medicament for the treatment of glioma, wherein the METTL inhibitor increases the drug sensitivity of temozolomide.
6. 6. A medicament for treating glioma, characterized in that the medicament composition as claimed in claim 3 or 4 is used as an active ingredient.
7. 7. The medicament of claim 6, further comprising pharmaceutically acceptable excipients.
8. 8. The medicament of claim 6, wherein the medicament is in the form of a solution.

Description

Use of METTL A inhibitor in preparation of product for improving sensitivity of glioma to temozolomide Technical Field The invention relates to the field of biological medicine, in particular to application of METTL inhibitor in preparation of a product for improving sensitivity of glioma to temozolomide. Background Glioblastoma (GBM) is a highly invasive brain tumor. Although Temozolomide (TMZ) is the standard treatment for glioblastoma, most patients develop resistance during the course of treatment, resulting in reduced efficacy. TMZ resistance is caused by a number of factors including DNA repair mechanisms, cell cycle regulation and alterations in the tumor microenvironment. Thus, overcoming resistance has become a challenge for GBM treatment. METTL 1A methyltransferase regulates translation, mainly by adding N7-methylguanosine (m 7G) to RNA molecules. Studies have shown that METTL a is aberrantly expressed in a variety of cancers and promotes the growth and survival of tumor cells by regulating RNA translation efficiency. In GBM METTL1 is likely to be involved in regulating chemotherapy resistance by affecting ribosomal function and protein synthesis, thus altering the response of tumor cells to chemotherapeutic drugs. In tumor cells, CSNK1E (casein kinase 1 epsilon) acts as a key member of the HIPPO signaling pathway, regulating cell proliferation, apoptosis and migration. CSNK1E expression and activity are closely related to the development and progression of tumors. However, no report has been made as to whether there is a regulatory relationship between METTL and CSNK1E, and whether CSNK1E is associated with resistance to TMZ by GBM patients. Thus, intensive research into this mechanism will help to discover new molecular targets and therapeutic strategies to increase the sensitivity of GBM patients to TMZ. Disclosure of Invention The invention aims to provide an application of METTL < 1 > inhibitor in preparing a product for improving the sensitivity of glioma to temozolomide, so as to solve the problems in the prior art, and the invention uses si-METTL < 1 > -1 with a nucleotide sequence shown as SEQ ID NO.1 and si-METTL < 1 > -3 with a nucleotide sequence shown as SEQ ID NO.2 as METTL < 1 > inhibitors, wherein the METTL < 1 > inhibitor not only can be used for diagnosing and treating glioma, but also can improve the sensitivity of glioma cells to temozolomide. In order to achieve the above object, the present invention provides the following solutions: the invention provides an application of METTL a inhibitor in preparing a product for improving sensitivity of glioma to temozolomide. The invention also provides a pharmaceutical composition comprising temozolomide and METTL inhibitor. Further, the METTL1 inhibitor is si-METTL1-1 with a nucleotide sequence shown as SEQ ID NO.1 or si-METTL1-3 with a nucleotide sequence shown as SEQ ID NO. 2. Further, the METTL1 inhibitor is si-METTL1-1 with a nucleotide sequence shown as SEQ ID NO.1 or si-METTL1-3 with a nucleotide sequence shown as SEQ ID NO. 2. The invention also provides application of the pharmaceutical composition in preparing medicines for treating glioma, and the METTL inhibitor improves the drug sensitivity of temozolomide. The invention also provides a medicine for treating glioma, which takes the medicine composition as an active ingredient. Further, the composition also comprises pharmaceutically acceptable auxiliary materials. Further, the dosage form of the medicine is solution. The invention discloses the following technical effects: according to the invention, the nucleotide sequences of si-METTL1-1 shown as SEQ ID NO.1 and si-METTL1-3 shown as SEQ ID NO.2 are used as METTL inhibitors, glioma drug sensitivity research is carried out, and experimental results show that the proliferation, migration and invasion capacities of glioma cells can be effectively reduced and the sensitivity of temozolomide in glioblastoma can be remarkably improved by using METTL1 inhibitors to interfere METTL1 expression. Therefore, METTL inhibitors can be used for diagnosis and treatment of glioma, and can also improve the sensitivity of glioma cells to temozolomide. The invention provides a new auxiliary product for improving the curative effect of the targeted drug and has wide application prospect. Drawings In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained according to these drawings without inventive effort for a person skilled in the art. FIG. 1 is a graph of the results of a clinical glioma sample and a public database-level expression and prognosis correlation analysis, wherein A is a pancancer expression profile analysis for demonstrating the effec