LncRNA PVT1 regulates VEGFC through inhibiting miR-128 in bladder cancer cells
LncRNA PVT1 regulates VEGFC through inhibiting miR-128 in bladder cancer cells
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LncRNA PVT1通过抑制膀胱癌细胞中的miR-128来调节VEGFC
DOI：
10.1002/jcp.26929
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发表时间：
2019-02-01
影响因子：
5.6
通讯作者：
Chen Hequn
中科院分区：
文献类型：
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作者：
Yu, Cui;Liu Longfei;Chen Hequn
长链非编码RNA PVT 1被认为是多种癌症中的癌基因。我们以前的研究表明，膀胱癌组织中PVT 1水平较高，与膀胱癌患者的临床进展和预后不良相关。生物信息学分析表明，PVT 1可能通过miR-128作为竞争性内源RNA（ceRNA）调节VEGFC表达。在这项研究中，我们证明了PVT 1表达水平影响膀胱癌细胞的增殖和迁移能力。此外，PVT 1基因敲低显著降低了裸鼠膀胱癌细胞的增殖能力。荧光素酶分析和RNA结合蛋白的免疫沉淀进行研究的潜在机制的ceRNA的调节PVT 1和VEGFC。结果显示，PVT 1转录物数量的增加直接与miR-128相互作用，从而降低miR-128与VEGFC 3 '-非翻译区的结合。这种作用抑制了miR-128对VEGFC mRNA的降解。总之，这些结果表明，PVT 1可能通过miR-218和VEGFC在膀胱癌肿瘤发生中发挥关键作用。因此，PVT 1可能成为膀胱癌诊断和治疗的一个新的生物标志物。
Long noncoding RNA PVT1 is considered to be an oncogene in multiple cancers. Our previous studies indicated that PVT1 levels were higher in bladder cancer tissue and correlated with clinical progression and poor prognosis in bladder cancer patients. A bioinformatics analysis showed that PVT1 may regulate VEGFC expression through miR-128 as a competing endogenous RNA (ceRNA). In this study, we demonstrated that PVT1 expression levels affect the proliferation and migration ability of bladder cancer cells. Moreover, PVT1 knockdown significantly decreased the proliferation capacity of bladder cancer cells in nude mice. Luciferase assays and RNA-binding protein immunoprecipitation were performed to investigate the potential mechanism of ceRNAs in the regulation of PVT1 and VEGFC. The results showed that the increased number of PVT1 transcripts interacted directly with miR-128 to decrease miR-128 binding to the VEGFC 3 '-untranslated region. This effect suppressed VEGFC mRNA degradation by miR-128. In conclusion, these results indicated that PVT1 might play a critical role in bladder cancer tumorigenesis via miR-218 and VEGFC. Therefore, PVT1 could be a new biomarker for bladder cancer diagnosis and therapy.