Presentation Authors: Xu Chen*, Ziyue Chen, Ruihui Xie, Ming Huang, Qianghua Zhou, Jingtong Zhang, Jian Huang, Tianxin Lin, Guangzhou, China, People's Republic of
Introduction: The prognosis for patients with bladder cancer (BCa) with lymph node (LN) metastasis is poor and is not improved by current treatments. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of Differentiation antagonizing non-protein coding RNA (DANCR) in BCa lymph node metastasis remains unclear.
Methods: The expression of DANCR was detected by qRT-PCR in 120 patients with BCa, and association of DANCR with clinicopathological features and prognosis was analyzed. In vitro and in vivo assays were performed to explore the biological effects of DANCR in BCa cells. Microarray, RNA pulldown, and luciferase assays were used to investigate the molecular mechanisms of DANCR.
Results: The lncRNA 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 LRPPRC to stabilize mRNA. Moreover, oncogenesis facilitated by DANCR was attenuated by anti-IL-11 antibody or a STAT3 inhibitor (BP-1-102).
Conclusions: Our data demonstrated 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.
Source of Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81825016, 81702523)