The prognosis for patients with bladder cancer (BCa) with lymph node (LN) metastasis is poor, and it is not improved by current treatments. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including BCa. However, the role of Differentiation antagonizing non-protein coding RNA (DANCR) in BCa LN metastasis remains unclear. In this study, we discover that DANCR was significantly upregulated in BCa tissues and cases with LN metastasis. DANCR expression was positively correlated with LN metastasis status, tumor stage, histological grade, and poor patient prognosis. Functional assays demonstrated that DANCR promoted BCa cell migration, invasion, and proliferation in vitro and enhanced tumor LN metastasis and growth in vivo. Mechanistic investigations revealed that DANCR activated IL-11-STAT3 signaling and increased cyclin D1 and PLAU expression via guiding leucine-rich pentatricopeptide repeat containing (LRPPRC) to stabilize mRNA. Moreover, oncogenesis facilitated by DANCR was attenuated by anti-IL-11 antibody or a STAT3 inhibitor (BP-1-102). In conclusion, our findings indicate that DANCR induces BCa LN metastasis and proliferation via an LRPPRC-mediated mRNA stabilization mechanism. DANCR may serve as a multi-potency target for clinical intervention in LN-metastatic BCa.
Keywords: DANCR; IL-11-STAT3 signaling; bladder cancer; lymph node metastasis; proliferation.
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