Jiang Yongming, Zhao Hui, Chen Yuxiao, Li Kangjian, Li Tianjie, Chen Jianheng, Zhang Baiyu, Guo Caifen, Qing Liangliang, Shen Jihong, Liu Xiaodong, Gu Peng
Department of Urology, The 1st Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
Department of Urology, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.
Cell Death Dis. 2021 Dec 4;12(12):1129. doi: 10.1038/s41419-021-04421-0.
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.
远处转移的发生是前列腺癌（PCa）患者死亡的主要原因。了解PCa转移的机制对于改善其预后至关重要。据报道，外泌体长链非编码RNA（lncRNA）在PCa转移中的作用尚未完全明确。在此，我们发现一种外泌体lncRNA HOXD-AS1在去势抵抗性前列腺癌（CRPC）细胞系来源的外泌体以及转移性PCa患者的血清外泌体中上调，这与其组织表达相关。进一步研究证实，外泌体HOXD-AS1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。机制上，外泌体HOXD-AS1被PCa细胞直接内化，作为竞争性内源RNA（ceRNA）调节miR-361-5p/FOXM1轴，从而促进PCa转移。此外，我们发现转移性PCa患者血清外泌体HOXD-AS1上调，尤其是那些高负荷疾病患者。并且它与Gleason评分、远处和淋巴结转移、前列腺特异性抗原（PSA）无复发生存率以及无进展生存期（PFS）密切相关。这为外泌体HOXD-AS1介导的miR-361-5p/FOXM1轴对PCa远处转移的调控提供了新的见解，并为指导转移性PCa的检测和治疗提供了一种有前景的液体活检生物标志物。
