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

Yibo Bian; Shufen Xu; Zhishuang Gao; Jie Ding; Chao Li; Zhiwei Cui; Haoyu Sun; Juan Li; Juan Pu; Keming Wang

doi:10.1016/j.canlet.2024.217004

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

Cancer Lett. 2024 Aug 1:596:217004. doi: 10.1016/j.canlet.2024.217004. Epub 2024 Jun 3.

Authors

Yibo Bian¹, Shufen Xu², Zhishuang Gao³, Jie Ding², Chao Li⁴, Zhiwei Cui⁵, Haoyu Sun⁵, Juan Li², Juan Pu⁶, Keming Wang⁷

Affiliations

¹ Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of digestive Disease, Fourth Military Medical University, Xi'an, 710032, China.
² Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
³ Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
⁴ Department of General Surgery, Zhongshan Hospital, Fudan University School of Medicine, Shanghai, 200032, China.
⁵ Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
⁶ Department of Oncology, Lianshui County People's Hospital, Huai'an, 223400, China. Electronic address: [email protected].
⁷ Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. Electronic address: [email protected].

PMID: 38838765
DOI: 10.1016/j.canlet.2024.217004

Abstract

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, N⁶ -adenosine-methyltransferase-like 3 (METTL3) upregulated the stabilization of ABHD11-AS1 through the m⁶A reader IGF2BP2. Our study highlights ABHD11-AS1 as a significant regulator in CRC and it may become a potential target in future CRC treatment.

Keywords: ABHD11-AS1; Colorectal cancer; FOXM1; IGF2BP2; TRIM21; Ubiquitin.

MeSH terms

Adenosine / analogs & derivatives
Animals
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / pathology
Disease Progression
Feedback, Physiological
Female
Ferroptosis* / genetics
Forkhead Box Protein M1* / genetics
Forkhead Box Protein M1* / metabolism
Gene Expression Regulation, Neoplastic*
Humans
Male
Mice
Mice, Nude
Prognosis
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism
Ribonucleoproteins* / genetics
Ribonucleoproteins* / metabolism
Serine Proteases

Substances

RNA, Long Noncoding
IGF2BP2 protein, human
Forkhead Box Protein M1
RNA-Binding Proteins
Ribonucleoproteins
FOXM1 protein, human
SS-A antigen
N-methyladenosine
ABHD11 protein, human
Adenosine
Serine Proteases