Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas

Abstract

Cytoplasmic polyadenylation element binding proteins (CPEBs) are auxiliary translational factors that associate with consensus sequences present in 3′UTRs of mRNAs, thereby activating or repressing their translation. Knowing that CPEBs are players in cell cycle regulation and cellular senescence prompted us to investigate their contribution to the molecular pathology of gliomas–most frequent of intracranial tumors found in humans. To this end, we performed methylation analyses in the promoter regions of CPEB1-4 and identified the CPEB1 gene to be hypermethylated in tumor samples. Decreased expression of CPEB1 protein in gliomas correlated with the rising grade of tumor malignancy. Abundant expression of CPEBs2-4 was observed in several glioma specimens. Interestingly, expression of CPEB3 positively correlated with tumor progression and malignancy but negatively correlated with protein phosphorylation in the alternatively spliced region. Our data suggest that loss of CPEB3 activity in high-grade gliomas is caused by expression of alternatively spliced variants lacking the B-region that overlaps with the kinase recognition site. We conclude that deregulation of CPEB proteins may be a frequent phenomenon in gliomas and occurs on the level of transcription involving epigenetic mechanism as well as on the level of mRNA splicing, which generates isoforms with compromised biological properties.

Decreased Expression of CPEB3 Predicts a Poor Prognosis in Patients with Melanoma: A Study Based on TCGA Data

“…For example, Lin et al reported that epigenetic silencing of CPEB3 can not only promote the proliferation of CRC cells but also inhibit the apoptosis of CRC cells, providing a new prognostic marker for CRC patients [ 10 ]. Similarly, Skubal et al [ 12 ] found that the progression and malignancy of glioma were positively correlated with the expression of CPEB3. Furthermore, Liu et al [ 19 ] indicate that CPEB3 expression levels can be used as a potential biomarker for HCC patient stratification, and more importantly, results from Tang et al [ 11 ] demonstrated that miR-452-3p directly targeted the CPEB3/EGFR axis and accelerated the proliferation and migration of liver cancer cells, which may provide a new therapeutic strategy for the treatment of HCC.…”

“…CPEB3 is a crucial modulator of cytoplasmic polyadenylation [ 10 ] and was downregulated in colorectal cancer (CRC) and ovarian clear cell adenocarcinoma [ 11 ]; therefore, it is considered to be a tumor suppressor. Skubal et al found that expression of CPEB3 was positively correlated with tumor progression and malignancy but negatively correlated with phosphorylation of CPEB3, which may be regarded as a marker for prolonged survival in glioma patients [ 12 ]. On the other hand, it has been found that CPEB3 inhibited the proliferation, migration, invasion, and apoptosis of hepatocellular carcinoma (HCC) cells, leading to G0/G1 arrest [ 11 ].…”

Bioinformatic Analysis of CPEB3 in Head and Neck Squamous Cell Carcinoma via mTOR Pathway and its microRNA Targets

“…Both types of biomarkers have their advantages and disadvantages (13) . https://www.indjst.org/ (14) . Glioma patients showed negative correlation of CPEB3 with survival of patients but positive correlation with cancer proliferation.…”

Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity

“…This result indicates that the hsa-mir-496 controls “adherens” cycle process under MG condition. The transcript ENST00000265997 encodes for Cytoplasmic polyadenylation element binding proteins (CPEBs) which is associated with cell cycle regulation and cellular senescence 34 . Another known miRNA hsa-mir-151a was significantly expressed in MG samples targeting the transcript, ENST00000292174 that encodes for C–X–C motif chemokine receptor protein.…”