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LncRNA BCAN-AS1stabilizes c-Myc via N6-methyladenosine-mediated binding with SNIP1 to promote pancreatic cancer
- Source :
- Cell Death and Differentiation; 20230101, Issue: Preprints p1-18, 18p
- Publication Year :
- 2023
-
Abstract
- C-Myc overexpression contributes to multiple hallmarks of human cancer but directly targeting c-Myc is challenging. Identification of key factors involved in c-Myc dysregulation is of great significance to develop potential indirect targets for c-Myc. Herein, a collection of long non-coding RNAs (lncRNAs) interacted with c-Myc is detected in pancreatic ductal adenocarcinoma (PDAC) cells. Among them, lncRNA BCAN-AS1is identified as the one with highest c-Myc binding enrichment. BCAN-AS1was abnormally elevated in PDAC tumors and high BCAN-AS1level was significantly associated with poor prognosis. Mechanistically, Smad nuclear-interacting protein 1 (SNIP1) was characterized as a new N6-methyladenosine (m6A) mediator binding to BCAN-AS1via recognizing its m6A modification. m6A-modified BCAN-AS1acts as a scaffold to facilitate the formation of a ternary complex together with c-Myc and SNIP1, thereby blocking S phase kinase-associated protein 2 (SKP2)-mediated c-Myc ubiquitination and degradation. Biologically, BCAN-AS1promotes malignant phenotypes of PDAC in vitro and in vivo. Treatment of metastasis xenograft and patient-derived xenograft mouse models with in vivo-optimized antisense oligonucleotide of BCAN-AS1effectively represses tumor growth and metastasis. These findings shed light on the pro-tumorigenic role of BCAN-AS1and provide an innovant insight into c-Myc-interacted lncRNA in PDAC.
Details
- Language :
- English
- ISSN :
- 13509047 and 14765403
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Cell Death and Differentiation
- Publication Type :
- Periodical
- Accession number :
- ejs64016239
- Full Text :
- https://doi.org/10.1038/s41418-023-01225-x