{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen C"],"funding":["National Natural Science Foundation of China","National Natural Science Foundation of Guangdong"],"pagination":["404-421"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6934220"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["130(1)"],"pubmed_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."],"journal":["The Journal of clinical investigation"],"pubmed_title":["Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer."],"pmcid":["PMC6934220"],"funding_grant_id":["2018A030313564","81572514","81472384","81825016","81472381"],"pubmed_authors":["Liu H","Li Y","Li J","Huang J","Lin T","He W","Zhong G","Luo Y","Chen C","Kong Y","Chen R","Zhao Y"],"additional_accession":[]},"is_claimable":false,"name":"Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2026-05-05T03:49:27.379Z","creation":"2025-04-20T02:01:07.642Z"},"accession":"S-EPMC6934220","cross_references":{"pubmed":["31593555"],"doi":["10.1172/jci130892","10.1172/JCI130892"]}}