Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer.
Direct regulation of LAMP1 by tumor-suppressive microRNA-320a in prostate cancer.
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DOI：
10.3892/ijo.2016.3522
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发表时间：
2016-07
影响因子：
5.2
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Okato A;Goto Y;Kurozumi A;Kato M;Kojima S;Matsushita R;Yonemori M;Miyamoto K;Ichikawa T;Seki N
晚期前列腺癌（PCa）转移到骨和淋巴结，目前可用的治疗方法不能阻止疾病的进展和转移。因此，需要使用当前的基因组方法来提高对晚期PCa进展和转移的分子机制的理解。我们在去势抵抗性前列腺癌（CRPC）中的miRNA表达特征显示，microRNA-320 a（miR-320 a）在癌组织中显著减少，表明miR-320 a可能是一种有前途的抗癌miRNA。本研究的目的是研究miR-320 a在幼稚PCa和CRPC细胞中的功能作用，并鉴定参与PCa转移的miR-320 a调节基因。miR-320 a的表达水平在未经处理的PCa、CRPC标本和PCa细胞系中显著降低。成熟miR-320 a在PCa细胞系中的恢复显示miR-320 a显著抑制癌细胞的迁移和侵袭。此外，我们发现溶酶体相关膜蛋白1（lysosomal-associated membrane protein 1，LAMP 1）是PCa细胞中miR-320 a的直接靶点。使用siRNA沉默LAMP 1显著抑制PCa细胞中的细胞增殖、迁移和侵袭。在PCa和CRPC临床标本中观察到LAMP 1的过表达。此外，使用si-LAMP 1转染的细胞鉴定下游途径。肿瘤抑制性miR-320 a介导的通路的发现可能为PCa转移的潜在机制提供重要见解。
Advanced prostate cancer (PCa) metastasizes to bone and lymph nodes, and currently available treatments cannot prevent the progression and metastasis of the disease. Therefore, an improved understanding of the molecular mechanisms of the progression and metastasis of advanced PCa using current genomic approaches is needed. Our miRNA expression signature in castration-resistant prostate cancer (CRPC) revealed that microRNA-320a (miR-320a) was significantly reduced in cancer tissues, suggesting that miR-320a may be a promising anticancer miRNA. The aim of this study was to investigate the functional roles of miR-320a in naïve PCa and CRPC cells and to identify miR-320a-regulated genes involved in PCa metastasis. The expression levels of miR-320a were significantly reduced in naïve PCa, CRPC specimens, and PCa cell lines. Restoration of mature miR-320a in PCa cell lines showed that miR-320a significantly inhibited cancer cell migration and invasion. Moreover, we found that lysosomal-associated membrane protein 1 (LAMP1) was a direct target of miR-320a in PCa cells. Silencing of LAMP1 using siRNA significantly inhibited cell proliferation, migration, and invasion in PCa cells. Overexpression of LAMP1 was observed in PCa and CRPC clinical specimens. Moreover, downstream pathways were identified using si-LAMP1-transfected cells. The discovery of tumor-suppressive miR-320a-mediated pathways may provide important insights into the potential mechanisms of PCa metastasis.