CircEZH2 miR-133b IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A modified CREB1 mRNA [miRNA-seq]

ABSTRACT: Background: Aberrant expression of circular RNAs contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. Methods: High throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer and adjacent normal tissues. A series of gain and loss of function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT PCR, western blot, luciferase reporter assays and MeRIP seq analysis were further applied to dissect the detailed mechanisms. Results: Here, a novel circRNA named circEZH2 , was screened out by RNA seq in CRC tissues, whose expression is related to clinicpathological characteristics and prognosis in CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination dependent degradation. Meanwhile, circEZH2 could serve as a competing endogenous RNA for miR 133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2 IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. Conclusions: Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2 miR 133b IGF2BP2 CREB1 regulatory axis to combat CRC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205094 | GEO | 2022/06/04

REPOSITORIES: GEO