LncRNA RP11-79H23.3 Functions as a Competing Endogenous RNA to Regulate PTEN Expression through Sponging hsa-miR-107 in the Development of Bladder Cancer
LncRNA RP11-79H23.3 Functions as a Competing Endogenous RNA to Regulate PTEN Expression through Sponging hsa-miR-107 in the Development of Bladder Cancer
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LncRNA RP11-79H23.3 在膀胱癌的发展过程中作为竞争性内源 RNA 通过海绵 hsa-miR-107 调节 PTEN 表达
DOI：
10.3390/ijms19092531
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发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
Chen, Junxia
中科院分区：
文献类型：
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作者：
Chi, Hong;Yang, Rui;Chen, Junxia
越来越多的证据表明，长链非编码rna （lncRNAs）的异常表达参与了肿瘤的发生和癌症的发展。然而，lncrna在膀胱癌（BC）中的生物学功能和潜在机制在很大程度上仍然未知。在这里，我们使用微阵列分析了BC中lncRNA和mRNA的表达谱。我们发现lncRNA RP11-79H23.3和磷酸酶和紧张素同源物（PTEN）在BC组织和细胞中显著下调。同时，RP11-79H23.3的表达与BC的临床分期呈负相关。在功能上，我们发现过表达RP11-79H23.3可以抑制细胞增殖、迁移和细胞周期进程，重新排列细胞骨架，并诱导细胞凋亡。此外，上调RP11-79H23.3抑制血管生成、肿瘤发生和肺转移，而下调RP11-79H23.3则发挥相反的作用。在机制上，我们发现RP11-79H23.3可以直接结合miR-107并消除对靶基因PTEN的抑制作用，从而导致PI3K/Akt信号通路失活。综上所述，我们首先证明了RP11-79H23.3可能通过作为miR-107增加PTEN表达的海绵来抑制BC的发病和发展。我们的研究表明，RP11-79H23.3可能是诊断和治疗BC的潜在靶点。
Accumulating evidence indicates that the aberrant expression of long noncoding RNAs (lncRNAs) is involved in tumorigenesis and cancer development. However, the biological functions and underlying mechanisms of lncRNAs in bladder cancer (BC) remain largely unknown. Here, we analyzed the lncRNA and mRNA expression profiles in BC using a microarray assay. We found that lncRNA RP11-79H23.3 and phosphatase and tensin homolog (PTEN) were significantly downregulated in BC tissues and cells. Meanwhile, RP11-79H23.3 expression was negatively correlated with clinical stage in BC. Functionally, we found that overexpression of RP11-79H23.3 could suppress cell proliferation, migration, and cell cycle progression, rearrange the cytoskeleton, and induce apoptosis in vitro. Moreover, upregulation of RP11-79H23.3 inhibited the angiogenesis, tumorigenesis, and lung metastasis in vivo, whereas RP11-79H23.3 knockdown exerted a contrary role. Mechanistically, we identified that RP11-79H23.3 could directly bind to miR-107 and abolish the suppressive effect on target gene PTEN, which leads to inactivation of the PI3K/Akt signaling pathway. Taken together, we first demonstrated that RP11-79H23.3 might suppress the pathogenesis and development of BC by acting as a sponge for miR-107 to increase PTEN expression. Our research revealed that RP11-79H23.3 could be a potential target for diagnosis and therapy of BC.