Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis.
Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis.
复制标题
外泌体长非编码RNA HOXD-AS1通过miR-361-5p/FOXM1轴促进前列腺癌转移
DOI：
10.1038/s41419-021-04421-0
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发表时间：
2021-12-04
影响因子：
9
通讯作者：
Gu P
中科院分区：
文献类型：
--
作者：
Jiang Y;Zhao H;Chen Y;Li K;Li T;Chen J;Zhang B;Guo C;Qing L;Shen J;Liu X;Gu P
远处转移的发展是前列腺癌（PCa）患者死亡的主要原因。了解PCa转移的机制对改善其预后至关重要。外泌体长链非编码RNA（lncRNA）在前列腺癌转移中的作用尚未完全阐明。在这里，我们发现外泌体lncRNA HOXD-AS 1在去势抵抗性前列腺癌（CRPC）细胞系来源的外泌体和来自转移性PCa患者的血清外泌体中上调，这与其组织表达相关。进一步的研究证实，外泌体HOXD-AS 1通过诱导转移相关表型在体外和体内促进前列腺癌细胞转移。外泌体HOXD-AS 1直接被PCa细胞内化，作为竞争性内源性RNA（ceRNA）调节miR-361- 5 p/FOXM 1轴，从而促进PCa转移。此外，我们发现，血清外泌体HOXD-AS 1在转移性PCa患者中上调，特别是那些具有高体积疾病的患者。与Gleason评分、远处转移、淋巴结转移、前列腺特异性抗原（PSA）无复发生存期、无进展生存期（PFS）密切相关。这为外泌体HOXD-AS 1介导的miR-361- 5 p/FOXM 1轴调控PCa远处转移提供了新的见解，并为指导转移性PCa的检测和治疗提供了有前途的液体活检生物标志物。
Development of distant metastasis is the main cause of deaths in prostate cancer (PCa) patients. Understanding the mechanism of PCa metastasis is of utmost importance to improve its prognosis. The role of exosomal long noncoding RNA (lncRNA) has been reported not yet fully understood in the metastasis of PCa. Here, we discovered an exosomal lncRNA HOXD-AS1 is upregulated in castration resistant prostate cancer (CRPC) cell line derived exosomes and serum exosomes from metastatic PCa patients, which correlated with its tissue expression. Further investigation confirmed exosomal HOXD-AS1 promotes prostate cancer cell metastasis in vitro and in vivo by inducing metastasis associated phenotype. Mechanistically exosomal HOXD-AS1 was internalized directly by PCa cells, acting as competing endogenous RNA (ceRNA) to modulate the miR-361-5p/FOXM1 axis, therefore promoting PCa metastasis. In addition, we found that serum exosomal HOXD-AS1 was upregulated in metastatic PCa patients, especially those with high volume disease. And it is correlated closely with Gleason Score, distant and nodal metastasis, Prostatic specific antigen (PSA) recurrence free survival, and progression free survival (PFS). This sheds a new insight into the regulation of PCa distant metastasis by exosomal HOXD-AS1 mediated miR-361-5p/FOXM1 axis, and provided a promising liquid biopsy biomarker to guide the detection and treatment of metastatic PCa.
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DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
3.7
作者：
Işın M;Uysaler E;Özgür E;Köseoğlu H;Şanlı Ö;Yücel ÖB;Gezer U;Dalay N
通讯作者：
Dalay N
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
21.3
作者：
Esposito M;Fang C;Cook KC;Park N;Wei Y;Spadazzi C;Bracha D;Gunaratna RT;Laevsky G;DeCoste CJ;Slabodkin H;Brangwynne CP;Cristea IM;Kang Y
通讯作者：
Kang Y
影响因子：
11.5
作者：
Chakraborty, Goutam;Armenia, Joshua;Kantoff, Philip W.
通讯作者：
Kantoff, Philip W.