SUMOylation of PUM2 promotes the vasculogenic mimicry of glioma cells via regulating CEBPD

Abstract

Glioma is the most common form of primary central nervous malignant tumors. Vasculogenic mimicry (VM) is a blood supply channel that is different from endothelial blood vessels in glioma. VM is related to tumor invasion and metastasis. Therefore, it plays an important role to target therapy for glioma VM. Our experimental results showed abnormal expression of UBE2I, PUM2, CEBPD, and DSG2 in glioma cells. The Co-IP and Immunofluorescence staining were used to detect that PUM2 can be modified by SUMO2/3. The interaction between PUM2 and CEBPD mRNA was detected by the RIP assays. The interaction between transcription factor CEBPD and promoter region of DSG2 was detected by the ChIP assays and luciferase assays. The capacity for migration in glioma cells was observed by the laser holographic microscope. The capacity for invasion in glioma cells was detected by Transwell method. The VM in glioma cells was detected by three-dimensional cell culture method. The experimental results found that the upregulation of UBE2I in glioma tissues and cells promotes the SUMOylation of PUM2, which decreases not only the stability of PUM2 protein but also decreases the inhibitory effect of PUM2 on CEBPD mRNA. The upregulation of CEBPD promotes the binding to the upstream promoter region of DSG2 gene, further upregulates the expression of DSG2, and finally promotes the development of glioma VM. In conclusion, this study found that the UBE2I/PUM2/CEBPD/DSG2 played crucial roles in regulating glioma This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

SUMOylation Regulator-Related Molecules Can Be Used as Prognostic Biomarkers for Glioblastoma

“…UBE2I is highly expressed in glioblastoma and promotes the SUMOylation of CRMP2, which in turn drives the proliferation of glioblastoma (Wang and Ji, 2019). Moreover, the upregulated UBE2I can promote the SUMOylation of PUM2 and ultimately promote glioma vasculogenic mimicry (Wang et al, 2020). However, other SUMOylation regulators are rarely reported in glioblastoma.…”

Cervical Cancer Development: Implications of HPV16 E6E7-NFX1-123 Regulated Genes

“…In our dysplasia and cervical cancer models, we focused our in vitro analyses on several genes of clinical and biologic interest. CEBPD is a bZIP transcription factor with immune response functions and varied roles in cell proliferation, differentiation, and apoptosis [ 29 ]. In addition to being highly expressed in premalignant and malignant cervical cancers ( Figure 2 and Figure 5 ), RNA levels were upregulated in HFKs with 16E6E7 expression and in the HPV16+ cervical cancer cell line, SiHa ( Figure 4 and Figure 6 A).…”

LOXL1‐AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR‐374b‐5p/MMP14 axis

“…Vasculogenic mimicry (VM), a newly discovered form of angiogenesis in which vessels are surrounded by tumour cells rather than vascular endothelial cells, is now gaining attention 5 . Several reports have discovered VM in diverse cancers, such as glioma, hepatocellular carcinoma, gastric cancer, non–small‐cell lung cancer and colorectal cancer 6–10 . VM has a close association with tumour metastasis and is a predictor of poor clinical prognosis 11,12 …”

“… 5 Several reports have discovered VM in diverse cancers, such as glioma, hepatocellular carcinoma, gastric cancer, non–small‐cell lung cancer and colorectal cancer. 6 , 7 , 8 , 9 , 10 VM has a close association with tumour metastasis and is a predictor of poor clinical prognosis. 11 , 12 …”

“…lung cancer and colorectal cancer. [6][7][8][9][10] VM has a close association with tumour metastasis and is a predictor of poor clinical prognosis. 11,12 RNA-binding proteins (RBPs) participate in tumour development, playing roles in pre-mRNA splicing, translation and RNA stabilization.…”