Effect Of WDR12 On Proliferation And Self-renewal Of Glioma Stem Cells

Tumor stem cells refer to a group of tumor cells in a tumor tissue that are capable of self-renewal,have multi-differentiation potential,and are highly tumorigenic.Glioma is a tumor of glial cells originating from the brain or spinal column.The patient accounts for 30% of the total number of brain tumor patients and 80% of malignant brain tumor patients.It is a research hotspot in the field of brain tumors.Types of glioma include,but are not limited to,astrocytoma,ependymoma,oligodendroglioma,and mixed glioma.As the disease progresses,the patient may develop symptoms of increased intracranial pressure and cause a series of symptoms.In the later stage of the disease,it often progresses to a malignant glioblastoma with high malignancy and invasive growth,which is difficult to treat by surgical resection.The effect of radiotherapy and chemotherapy is also unsatisfactory.Clinical recurrence is very common.The median survival time is around 15 months.Glioma stem cells(GSC)have the characteristics of insensitivity to radiotherapy and chemotherapy,multi-differentiation potential and self-renewal ability,and are considered to be the main cause of glioma occurrence,development and resistance to various treatments and even recurrence.Therefore,research on glioma stem cell GSC will help us fight this malignant disease more effectively.The author's laboratory has long been focused on the research on the regulation of tumor stem cells on tumorigenesis,development and treatment transformation,and has accumulated certain experience in this field.In order to identify specific high-expression proteins in GSC,we compared the protein expression differences between GSC and its corresponding non-stem tumor cells(NSTC)by mass spectrometry,and found a series of proteins with large differences in expression between GSC and NSTC.Combined with clinical data analysis of glioblastoma in Rembrandt,a brain tumor database of NCI in the United States,we found that the WDR12 gene is highly expressed in tumor tissues of glioma patients and low in normal brain tissues.At the same time,with the increase of the malignant degree of glioma in patients,the expression of WDR12 protein in tumor tissues of glioma patients also increased.Further,in the clinical prognostic correlation analysis of the database,we also found that patients with gliomas with high expression of WDR12 had a significantly poorer prognosis.These results together show that WDR12 protein may play an important role in the development of glioma.WDR12 is a member of the WDR12/YTM1 family of WD repeat proteins,which together with Pes1 and Bop1 form a stable complex called PeBoW,which is involved in the maturation of ribosomal subunits and is a key protein essential for ribosomal biogenesis and cell proliferation.However,there has been no literature on the expression and function of WDR12 in glioma stem cells.We conducted a series of studies on the WDR12 gene in the GSC to explore the function and mechanism of WDR12 in GSC.In the study,we found that:(1)the expression of WDR12 in GSC is significantly higher than that in non-stem tumor cells;(2)the higher the degree of malignancy of glioma,the higher the expression level of WDR12 in tumor tissues;(3)knockdown of WDR12 expression in GSC significantly inhibited the proliferation and self-renewal ability of GSC;(4)knockdown of WDR12 expression in GSC significantly inhibited the growth of orthotopic transplanted tumor in tumor-bearing mice,and prolonged tumor growth Mouse life cycle.These results suggest that the WDR12 gene may play an important role in the proliferation and self-renewal of GSC and in the development and progression of glioma.In future experiments,we will further study the specific mechanism of WDR12 function in GSC,hoping to provide clues for the targeted treatment of clinical glioma.