1. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer
- Author
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Chen, Changhao, Luo, Yuming, He, Wang, Zhao, Yue, Kong, Yao, Liu, Hongwei, Zhong, Guangzheng, Li, Yuting, Li, Jun, Huang, Jian, Chen, Rufu, and Lin, Tianxin
- Subjects
Vascular endothelial growth factor -- Health aspects ,Cancer metastasis -- Prognosis -- Health aspects ,Antisense RNA -- Health aspects ,Endothelium ,Endothelial growth factors ,RNA ,Tumors ,Cancer patients ,Health care industry - Abstract
Patients with bladder cancer (BCa) with clinical lymph node (LN) metastasis have an extremely poor prognosis. VEGF-C has been demonstrated to play vital roles in LN metastasis in BCa. However, approximately 20% of BCa with LN metastasis exhibits low VEGF-C expression, suggesting a VEGF-C-independent mechanism for LN metastasis of BCa. Herein, we demonstrate that BCa cell-secreted exosome-mediated lymphangiogenesis promoted LN metastasis in BCa in a VEGF-C-independent manner. We identified an exosomal long noncoding RNA (lncRNA), termed lymph node metastasis-associated transcript 2 (LNMAT2), that stimulated human lymphatic endothelial cell (HLEC) tube formation and migration in vitro and enhanced tumor lymphangiogenesis and LN metastasis in vivo. Mechanistically, LNMAT2 was loaded to BCa cell-secreted exosomes by directly interacting with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1). Subsequently, exosomal LNMAT2 was internalized by HLECs and epigenetically upregulated prospero homeobox 1 (PROX1) expression by recruitment of hnRNPA2B1 and increasing the H3K4 trimethylation level in the PROX1 promoter, ultimately resulting in lymphangiogenesis and lymphatic metastasis. Therefore, our findings highlight a VEGF-C-independent mechanism of exosomal lncRNA-mediated LN metastasis and identify LNMAT2 as a therapeutic target for LN metastasis in BCa., Introduction Bladder cancer (BCa), one of the most commonly diagnosed malignancies worldwide, is the leading cause of cancer-related death among men, with an estimated 550,000 new cases and 20,000 deaths [...]
- Published
- 2020
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