DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression
DANCR Promotes Metastasis and Proliferation in Bladder Cancer Cells by Enhancing IL-11-STAT3 Signaling and CCND1 Expression
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DANCR 通过增强 IL-11-STAT3 信号传导和 CCND1 表达促进膀胱癌细胞的转移和增殖
DOI：
10.1016/j.ymthe.2018.12.015
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发表时间：
2019-02-06
影响因子：
12.4
通讯作者：
Lin, Tianxin
中科院分区：
文献类型：
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作者：
Chen, Ziyue;Chen, Xu;Lin, Tianxin
膀胱癌淋巴结转移患者的预后较差，目前的治疗方法不能改善其预后。长链非编码RNA（lncRNA）参与包括BCa在内的各种肿瘤的病理学。然而，分化拮抗非蛋白编码RNA（DANCR）在BCa LN转移中的作用尚不清楚。在这项研究中，我们发现DANCR在BCa组织和LN转移病例中显著上调。DANCR表达与LN转移状态、肿瘤分期、组织学分级和患者预后不良呈正相关。功能分析表明，DANCR在体外促进BCa细胞的迁移、侵袭和增殖，在体内促进肿瘤LN的转移和生长。机制研究表明，DANCR通过引导富含亮氨酸的五肽重复序列（LRPPRC）稳定mRNA，激活IL-11-STAT 3信号通路，增加细胞周期蛋白D1和PLAU的表达。此外，抗IL-11抗体或STAT 3抑制剂（BP-1-102）可减弱DANCR促进的肿瘤发生。总之，我们的研究结果表明，DANCR通过LRPPRC介导的mRNA稳定机制诱导BCa LN转移和增殖。DANCR可作为LN转移性BCa临床干预的多潜能靶点。
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.