Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Biochem Biophys Res Commun. 2014 Jun 27;449(2):190-5. doi: 10.1016/j.bbrc.2014.04.140. Epub 2014 May 4.
Previous studies have shown that miR-214 functions either as an oncogene or a tumor suppressor in various human cancer types. The role of this microRNA in osteosarcoma (OS) is presently unclear. Here, we demonstrated that miR-214 is frequently upregulated in OS specimens, compared with noncancerous bone tissues. Bioinformatics analysis further revealed leucine zipper, putative tumor suppressor 1 (LZTS1) as a potential target of miR-214. Expression patterns of miR-214 were inversely correlated with those of LZTS1 mRNA and protein in OS tissues. Data from reporter assays showed that miR-214 directly binds to the 3'-untranslated region (3'-UTR) of LZTS1 mRNA and suppresses expression at both transcriptional and translational levels. In functional assays, miR-214 promoted OS cell proliferation, invasion and tumor growth in nude mice, which could be reversed by overexpression of LZTS1. Taken together, our data provide compelling evidence that miR-214 functions as an onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of LZTS1.
先前的研究表明，miR-214 在各种人类癌症类型中既可以作为癌基因，也可以作为肿瘤抑制因子发挥作用。这种 microRNA 在骨肉瘤（OS）中的作用目前尚不清楚。在这里，我们证明与非癌性骨组织相比，miR-214 在 OS 标本中经常上调。生物信息学分析进一步显示亮氨酸拉链、潜在肿瘤抑制因子 1（LZTS1）是 miR-214 的潜在靶标。OS 组织中 miR-214 的表达模式与 LZTS1 mRNA 和蛋白的表达模式呈负相关。来自报告基因检测的数据表明，miR-214 可直接结合 LZTS1 mRNA 的 3'-非翻译区（3'-UTR），并在转录和翻译水平上抑制其表达。在功能检测中，miR-214 促进 OS 细胞的增殖、侵袭和裸鼠肿瘤生长，而 LZTS1 的过表达可逆转这一现象。综上所述，我们的数据提供了令人信服的证据，表明 miR-214 在 OS 中作为致癌 miRNA 发挥作用，其致癌作用主要是通过下调 LZTS1 来介导的。
