Journal
MOLECULAR THERAPY
Volume 27, Issue 2, Pages 326-341Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2018.12.015
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81702523, 81825016, 81772719, 81772728, 81572514, 81472384]
- National Natural Science Foundation of Guangdong [2016A030313321, 2016A030313244, 2015A030311011]
- Science and Technology Program of Guangzhou [201804010041, 201604020156, 201604020177]
- Science and Technology Planning Project of Guangdong Province [2017B020227007]
- Guangdong Special Support Program [2017TX04R246]
- Fundamental Research Funds for the Central Universities [18ykpy18]
- Guangdong Province Higher Vocational Colleges & Schools Pearl River Scholar Funded Scheme
- Yat-Sen Scholarship for Young Scientist
- Sun Yat-sen Initiative Program for Scientific Research [YXQH201708]
- Cultivation of Major Projects and Emerging, Interdisciplinary Fund, Sun Yat-Sen University [16ykjc18]
- National Clinical Key Specialty Construcion Project for Department of Urology
- Department of Oncology
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University [KLB09001]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available