Wan Yueping, Zeng Zhao-chang, Xi Ming, Wan Song, Hua Wei, Liu Yuan-ling, Zhou Yu-lin, Luo Hong-wei, Jiang Fu-neng, Zhong Wei-de
Department of Urology, Huadu District People's Hospital, Southern Medical University,Guangzhou 510800, China.
Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China.
Hum Pathol. 2015 Feb;46(2):295-303. doi: 10.1016/j.humpath.2014.10.027. Epub 2014 Nov 26.
Our previous study revealed that microRNA (miR)-224 down-regulation could promote tumor progression of prostate cancer (PCa) and might be associated with poor biochemical recurrence-free survival of patients with this malignancy. However, the underlying mechanisms of miR-224 have not been fully elucidated. In the current study, apelin (APLN) was identified as a target gene of miR-224. Forced expression of miR-224 inhibited PCa cell invasion and migration by suppressing the expression of APLN. In addition, the down-regulation of miR-224 was negatively correlated with the up-regulation of APLN mRNA in PCa tissues. Moreover, miR-224 down-regulation was significantly associated with advanced clinical stage (P = .027) and metastasis (P = .001), whereas APLN up-regulation more frequently occurred in PCa tissues with advanced pathologic stage (P = .003), metastasis (P < .001), and prostate-specific antigen failure (P = .001). Furthermore, patients with PCa in the miR-224-low/APLN-high group more frequently had shorter biochemical recurrence-free survival than those in groups with other expression patterns of the 2 molecules. Taken together, our data strongly confirmed for the first time that the dysregulated miR-224/APLN axis may be associated with tumorigenesis and aggressive progression of PCa. More importantly, miR-224 down-regulation and APLN up-regulation may synergistically predict biochemical recurrence-free survival in patients with PCa.
我们之前的研究表明，微小RNA（miR）-224表达下调可促进前列腺癌（PCa）的肿瘤进展，且可能与该恶性肿瘤患者生化无复发生存期短有关。然而，miR-224的潜在机制尚未完全阐明。在本研究中，apelin（APLN）被确定为miR-224的靶基因。miR-224的强制表达通过抑制APLN的表达来抑制PCa细胞的侵袭和迁移。此外，miR-224下调与PCa组织中APLN mRNA上调呈负相关。而且，miR-224下调与晚期临床分期（P = 0.027）和转移（P = 0.001）显著相关，而APLN上调在病理分期晚期（P = 0.003）、有转移（P < 0.001）和前列腺特异性抗原失败（P = 0.001）的PCa组织中更常见。此外，miR-224低/APLN高组的PCa患者比其他这两种分子表达模式组合组的患者更频繁地出现生化无复发生存期短的情况。综上所述，我们的数据首次有力地证实，失调的miR-224/APLN轴可能与PCa的肿瘤发生和侵袭性进展有关。更重要的是，miR-224下调和APLN上调可能协同预测PCa患者的生化无复发生存期。
