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CN-122012712-A - Use of MIDN in glioma diagnosis and treatment

CN122012712ACN 122012712 ACN122012712 ACN 122012712ACN-122012712-A

Abstract

The invention relates to the technical field of biomedicine, and particularly discloses application of MIDN protein in glioma diagnosis and treatment. Glioblastoma (GBM) is the most common malignant glioma in the central nervous system, and accounts for more than 50% of all gliomas, and the existing treatment means face the challenges of high drug resistance, poor prognosis and the like. Based on the association of protein degradation disorder and tumorigenesis development, MIDN can grasp substrate protein through a Catch domain, and degrade oncogenic substrate molecules (such as PPDPF) through a non-ubiquitin proteasome pathway, so that malignant progress of glioma is inhibited.

Inventors

  • Zou Hecun
  • ZHANG YANCHEN

Assignees

  • 重庆医科大学

Dates

Publication Date
20260512
Application Date
20260210

Claims (9)

  1. 1. The application of MIDN in glioma diagnosis and treatment, wherein glioma is glioblastoma GBM, is characterized in that the existence or malignancy degree of glioma is estimated by detecting the expression level of MIDN in a biological sample.
  2. 2. The application of MIDN protein in glioma treatment, wherein glioma is glioblastoma GBM, and is characterized in that glioma cell proliferation is inhibited by regulating MIDN expression or activity.
  3. 3. The method of claim 2, wherein said modulating MIDN expression comprises over-expressing MIDN or using a MIDN agonist.
  4. 4. Use of MIDN to PPDPF interactions in glioma diagnosis and treatment, characterized in that glioma is diagnosed or therapeutic efficacy is assessed by detecting the level of interaction of MIDN with PPDPF.
  5. 5. A method for constructing MIDN knockdown or over-expression glioma cell line is characterized in that siRNA or vector transfection technology is utilized to regulate and control the expression of MIDN in glioma cells U251, U87 or Hs683 of different types.
  6. 6. A glioma therapeutic drug based on MIDN degradation PPDPF is characterized by comprising MIDN protein or an active fragment thereof and is used for promoting PPDPF degradation.
  7. 7. A method of screening for compounds that target the MIDN-PPDPF pathway, characterized in that the effect of the compound on MIDN interaction or degradation with PPDPF is assessed by in vitro or in vivo models.
  8. 8. Use of MIDN as a biomarker in the prognosis evaluation of gliomas, characterized in that the patient survival is predicted in combination with the MIDN and PPDPF expression levels.
  9. 9. A therapeutic composition comprising MIDN genes for use in gene therapy of gliomas, wherein MIDN genes are delivered by viral vectors.

Description

Use of MIDN in glioma diagnosis and treatment Technical Field The invention relates to the field of biomedicine, in particular to an application of MIDN in glioma diagnosis and treatment. Background Glioblastoma (Glioblastoma, GBM) is a malignancy located in the central nervous system. 95% of central nervous system malignancies occur in the brain, with 75% from glial cells and GBM accounting for more than 50% of all gliomas. Protein degradation disorder is closely related to tumorigenesis and development, and in recent years, MIDN is found to realize ubiquitination independent degradation through a proteasome pathway, and the protein degradation disorder is possibly involved in tumor regulation. In the prior art, glioma has limited treatment means and outstanding drug resistance. MIDN have not yet been clarified as to the role in different tumors, and in particular, the functional mechanism in gliomas has yet to be explored. Based on the background, the invention provides a new application of MIDN in glioma diagnosis and treatment. Disclosure of Invention The invention aims to solve the defects in the prior art, and provides an application of MIDN in glioma diagnosis and treatment. In order to achieve the above purpose, the present invention adopts the following technical scheme: The application of MIDN in glioma diagnosis and treatment, wherein glioma is glioblastoma GBM, is characterized in that the existence or malignancy degree of glioma is estimated by detecting the expression level of MIDN in a biological sample. The application of MIDN protein in glioma treatment, wherein glioma is glioblastoma GBM, and is characterized in that glioma cell proliferation is inhibited by regulating MIDN expression or activity. Preferably, the means of modulating MIDN expression comprises over-expression MIDN or the use of MIDN agonists. Use of MIDN to PPDPF interactions in glioma diagnosis, to diagnose glioma or to evaluate the effect of a treatment by detecting the level of interaction of MIDN with PPDPF. A method for constructing MIDN knockdown or over-expression glioma cell line utilizes siRNA or vector transfection technology to regulate and control the expression of MIDN in different types of glioma cells U251, U87 or Hs683 cells. A glioma therapeutic based on MIDN degradation PPDPF comprising MIDN protein or an active fragment thereof for promoting PPDPF degradation. A method of screening for compounds that target the MIDN-PPDPF pathway by assessing the effect of the compound on MIDN interaction or degradation with PPDPF by an in vitro or in vivo model. Use of MIDN as a biomarker in the prognostic evaluation of gliomas, in combination with MIDN and PPDPF expression levels to predict patient survival. A therapeutic composition comprising MIDN genes for use in gene therapy of gliomas, delivering MIDN genes by viral vectors. The beneficial effects of the invention are as follows: MIDN serving as a novel cancer inhibiting factor can inhibit malignant progress of glioma through targeting degradation of PPDPF and other molecules, and provides a novel strategy for clinical diagnosis and treatment. (Can be added: PPDPF was found in glioma cells in the pro-cancerous effect, and PPDPF was studied and reported as MIDN substrate protein). Drawings FIG. 1 is a schematic representation of glioma epidemiological data showing the GBM in glioma; FIG. 2 is a MIDN knockdown efficiency verification graph, wherein the knockdown effect of MIDN in U251 and U87 cells is shown by Western blot; FIG. 3 shows that the proliferation of glioma cells is promoted after MIDN expression is reduced through CCK8 cell proliferation experiments and cell cycle experiments; FIG. 4 is a verification chart of MIDN over-expression efficiency, and shows MIDN over-expression effects in U87 and Hs683 cells through Western blot; FIG. 5 shows that MIDN inhibits glioma cell proliferation after up-regulation of expression by CCK8 cell proliferation and cell cycle experiments and clone formation experiments; FIG. 6 inhibition of glioma cell proliferation following knockdown PPDPF protein expression in U87 cells; FIG. 7 promotion of glioma cell proliferation following overexpression of PPDPF protein in U87 cells; FIG. 8 shows the interaction MIDN with its substrate protein PPDPF and with the proteasome core regulatory subunit PSMD2 in a U87 cell line; FIG. 9 MIDN is able to promote PPDPF protein degradation; FIG. 10 MIDIN is capable of inhibiting PPDPF proliferation-promoting effects on glioma cells. Detailed Description The technical scheme of the invention is further described in detail below with reference to the specific embodiments. In the description of the present invention, it should be noted that, unless explicitly stated and limited otherwise, the terms "mounted," "connected," and "disposed" are to be construed broadly, and may be, for example, fixedly connected, disposed, detachably connected, disposed, or integrally connected and disposed. The specific