LncRNA DANCR promotes ABL2-mediated metastasis via decoying of miR-125a-5p in high-risk neuroblastoma

Mingyou Gao¹Fang Cao¹Junling Li²Jun Zhang²Yuren Xia¹Xiangdong Tian¹Jie Li¹Daowei Wang¹Lin Lu¹Yan Guo¹Yuanyuan Liu²Qiang Zhao^1*Yun Liu¹

• ¹Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
• ²Tianjin Medical University, Tianjin, China

Patients with high-risk neuroblastoma preferentially present with widespread metastasis and often relapse despite intensive therapy, which is the major cause of death of patients with this cancer. Consequently, identifying the molecular drivers of neuroblastoma metastasis holds significant clinical importance. Here, high-throughput sequencing analysis revealed that the long noncoding RNA DANCR was significantly upregulated in high-risk neuroblastoma patients, and its expression correlated with poor prognosis. In vitro functional experiments demonstrated that DANCR promotes the proliferation, migration and invasion of neuroblastoma cells. Moreover, DANCR knockdown inhibited tumor metastasis in vivo. Integrative transcriptomic and pathway enrichment analyses further revealed that DANCR overexpression affects the actin cytoskeleton regulatory pathway. Mechanistically, DANCR functions as an oncogenic competing endogenous RNA (ceRNA) through high-affinity binding to miR-125a-5p, thereby promoting ABL2 expression. This DANCR-mediated regulation promotes the interaction between ABL2 and the cytoskeletal regulator cortactin, which leads to activation of the SSH1-cofilin pathway and then facilitates the formation of plate pseudopods, cytoskeletal reorganization and the metastatic ability of tumors. In summary, our findings delineate the DANCR/miR-125a-5p/ABL2/cofilin axis as a critical regulator of cytoskeletal dynamics in neuroblastoma metastasis, offering novel insights for the diagnosis and therapeutic targeting of high-risk neuroblastoma.