MicroRNA-3648 Is Upregulated to Suppress TCF21, Resulting in Promotion of Invasion and Metastasis of Human Bladder Cancer
MicroRNA-3648 Is Upregulated to Suppress TCF21, Resulting in Promotion of Invasion and Metastasis of Human Bladder Cancer
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MicroRNA-3648上调抑制TCF21促进人膀胱癌的侵袭和转移
DOI：
10.1016/j.omtn.2019.04.006
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发表时间：
2019-06-07
影响因子：
8.8
通讯作者：
Huang, Haishan
中科院分区：
文献类型：
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作者：
Sun, Wenrui;Li, Shi;Huang, Haishan
虽然microRNAs（miRNAs）在癌症中的潜力是众所周知的，但miR-3648的功能和机制在任何类型的癌症中几乎都没有被探索过。我们在此表明，与邻近的非肿瘤组织相比，miR-3648在人BC组织中上调。功能研究表明，在人侵袭性BC UMUC 3和T24 T细胞系中抑制miR-3648表达可降低体外迁移和侵袭，并抑制体内肺转移，而miR-3648过表达可促进BC细胞迁移和侵袭。生物信息学筛选和mRNA 3' UTR荧光素酶报告基因分析表明，转录因子21（TCF 21）是miR-3648的直接靶点，使用miR-3648抑制剂获得的结果显示，miR-3648通过降低其mRNA稳定性来抑制TCF 21蛋白表达。此外，Kisspeptin 1（KISS 1）被鉴定为负责miR-3648介导的BC侵袭和肺转移的TCF 21下游效应物。总体而言，本研究结果表明，miR-3648过表达，并通过指导TCF 21/KISS 1轴在介导BC侵袭和转移中发挥致癌作用，揭示miR-3648作为BC预后的潜在生物标志物和BC治疗的靶点。
Although microRNAs (miRNAs) are well-known for their potential in cancer, the function and mechanisms of miR-3648 have barely been explored in any type of cancer. We show here that miR-3648 is upregulated in human BC tissues in comparison with adjacent non-tumor tissues. Functional studies showed that inhibition of miR-3648 expression in the human invasive BC UMUC3 and T24T cell lines decreased migration and invasion in vitro and suppressed lung metastasis in vivo, whereas miR-3648 overexpression promoted BC cell migration and invasion. A bioinformatics screen and mRNA 3' UTR luciferase reporter assay showed that transcription factor 21 (TCF21) was a direct target of miR-3648, and the results obtained from using a miR-3648 inhibitor revealed that miR-3648 inhibited TCF21 protein expression by reduction of its mRNA stability. Further, Kisspeptin 1 (KISS1) was identified as a TCF21 downstream effector responsible for miR-3648-mediated BC invasion and lung metastasis. Collectively, the present results suggest that miR-3648 is overexpressed and plays an oncogenic role in mediation of BC invasion and metastasis through directing the TCF21/KISS1 axis, revealing miR-3648 as a potential biomarker for BC prognosis and a target for BC therapy.