C-Myc的过度表达对人类癌症具有多个特征的贡献，但是直接靶向C-Myc是具有挑战性的。鉴定参与C-Myc调控的关键因子对于开发C-Myc潜在间接靶点具有重要意义。在胰腺导管腺癌（PDAC）细胞中检测到与C-Myc相互作用的一组长非编码RNA（lncRNA）。其中，lncRNA BCAN-AS1被确定为具有最高C-Myc结合富集度的RNA。BCAN-AS1在PDAC肿瘤中异常升高，并且高水平的BCAN-AS1与不良预后显著相关。在机制上，Smad核蛋白相互作用蛋白1（SNIP1）被鉴定为一个新的N6-腺苷甲基化（m6A）介质，通过识别其m6A修饰结合到BCAN-AS1上。m6A修饰的BCAN-AS1作为一个支架促进与C-Myc和SNIP1形成三元复合物，从而阻断S期激酶相关蛋白2（SKP2）介导的C-Myc泛素化和降解。在生物学上，BCAN-AS1促进了PDAC的恶性表型在体内和体外。对转移性异种移植和患者源性异种移植小鼠模型进行用最佳化的BCAN-AS1反义寡核苷酸的治疗有效地抑制了肿瘤的生长和转移。这些发现揭示了BCAN-AS1在PDAC中的促肿瘤作用，并为C-Myc相互作用的lncRNA提供了一种创新的视角。© 2023. 作者（们）排他性许可给ADMC Associazione Differenziamento e Morte Cellulare。

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-AS1 is identified as the one with highest c-Myc binding enrichment. BCAN-AS1 was abnormally elevated in PDAC tumors and high BCAN-AS1 level 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-AS1 via recognizing its m6A modification. m6A-modified BCAN-AS1 acts 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-AS1 promotes 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-AS1 effectively represses tumor growth and metastasis. These findings shed light on the pro-tumorigenic role of BCAN-AS1 and provide an innovant insight into c-Myc-interacted lncRNA in PDAC.© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.