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.
基金:
National Natural Science Foundation
of China (Grant No. 81802548, 81860451), Yunnan Natural Science Foundation (Grant
No. 202001AW070001), Yunnan Health Training Project of High-Level Talents (for
Peng Gu, Grant No. H2018070), Provincial Natural Science Foundation of YunnanKunming Medical University Joint Foundation (Grant No. 2019FE001-136), Scientific
Research Project of Yunnan Provincial Educational Department (Grant No.
2018JS208). Funding for young doctors (for Peng Gu) from the 1st Affiliated Hospital
of Kunming Medical University (Grant No. 2017BS016).
第一作者机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Urol, Kunming 650032, Yunnan, Peoples R China[2]Kunming Med Univ, Affiliated Hosp 2, Dept Urol, Kunming 650101, Yunnan, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Med Univ, Affiliated Hosp 1, Dept Urol, Kunming 650032, Yunnan, Peoples R China[3]Yunnan Prov Clin Res Ctr Chron Kidney Dis, Kunming 650032, Yunnan, Peoples R China
推荐引用方式(GB/T 7714):
Jiang Yongming,Zhao Hui,Chen Yuxiao,et al.Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis[J].CELL DEATH & DISEASE.2021,12(12):doi:10.1038/s41419-021-04421-0.
APA:
Jiang, Yongming,Zhao, Hui,Chen, Yuxiao,Li, Kangjian,Li, Tianjie...&Gu, Peng.(2021).Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis.CELL DEATH & DISEASE,12,(12)
MLA:
Jiang, Yongming,et al."Exosomal long noncoding RNA HOXD-AS1 promotes prostate cancer metastasis via miR-361-5p/FOXM1 axis".CELL DEATH & DISEASE 12..12(2021)