m6A modification of lncRNA ABHD11-AS1 promotes colorectal cancer progression and inhibits ferroptosis through TRIM21/IGF2BP2/ FOXM1 positive feedback loop

Long non-coding RNA (lncRNA) is closely related to a variety of human cancers, which may provide huge potential biomarkers for cancer diagnosis and treatment. However, the aberrant expression of most lncRNAs in colorectal cancer (CRC) remains elusive. This study aims to explore the clinical significance and potential mechanism of lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) in the colorectal cancer. Here, we demonstrated that lncRNA ABHD11-AS1 is high-expressed in colorectal cancer (CRC) patients, and strongly related with poor prognosis. Functionally, ABHD11-AS1 suppresses ferroptosis and promotes proliferation and migration in CRC both in vitro and in vivo. Mechanically, lncRNA ABHD11-AS1 interacted with insulin-like growing factor 2 mRNA-binding protein 2 (IGF2BP2) to enhance FOXM1 stability, forming an ABHD11-AS1/FOXM1 positive feedback loop. E3 ligase tripartite motif containing 21 (TRIM21) promotes the degradation of IGF2BP2 via the K48-ubiquitin-lysosome pathway and ABHD11-AS1 promotes the interaction between IGF2BP2 and TRIM21 as scaffold platform. Furthermore, N 6 -adenosine-methyltransferase-like 3 (METTL3) upregulated the stabilization of ABHD11-AS1 through the m 6 A reader IGF2BP2. Our study highlights ABHD11-AS1 as a significant regulator in CRC and it may become a potential target in future CRC treatment. • ABHD11-AS1 is upregulated in human CRC tissues and related to poor prognosis • ABHD11-AS1 promotes CRC cell proliferation and suppresses ferroptosis • ABHD11-AS1 interacts with IGF2BP2 and affects CRC development through enhancing FOXM1 stability • ABHD11-AS1 promotes IGF2BP2 ubiquitination and degradation via E3 ligase TRIM21 • TRIM21 facilitates IGF2BP2 ubiquitination and ABHD11-AS1 promotes the interaction between IGF2BP2 and TRIM21 as scaffold platform • ABHD11-AS1 is upregulated by m 6 A modification and facilitates CRC development through a positive feedback loop with FOXM1