Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma
Highly Expressed miR-375 is not an Intracellular Oncogene in Merkel Cell Polyomavirus-Associated Merkel Cell Carcinoma
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DOI：
10.3390/cancers12030529
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发表时间：
2020-03-01
期刊：
影响因子：
5.2
通讯作者：
Becker, Juergen C.
中科院分区：
文献类型：
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作者：
Fan, Kaiji;Zebisch, Armin;Becker, Juergen C.
miR-375 是默克尔细胞癌 (MCC) 中高度丰富的 miRNA。在其他癌症中，它充当肿瘤抑制基因或癌基因。虽然自由循环的 miR-375 可作为晚期 MCC 患者肿瘤负荷的替代标志物，但其在 MCC 细胞内的功能尚未确定。使用 antagomiR 通过核转染实现了 MCC 细胞系中几乎完全的 miR-375 敲低。细胞活力、生长特性和形态并未因这种敲低而改变。使用 RNA 相互作用百科全书 (ENCORI) 确定了 miR-375 靶基因和相关信号通路，揭示了 Hippo 信号传导和上皮间质转化 (EMT) 相关基因可能受到调节。因此，在 miR-375 敲低后，通过多重 qRT-PCR 分析它们的表达，表明表达仅发生有限的变化。总之，经典 MCC 细胞系中高效的 miR-375 敲低并没有显着改变细胞活力、形态或致癌信号通路。这些观察结果表明 miR-375 不太可能是 MCC 细胞中的细胞内癌基因，因此表明 miR-375 在 MCC 细胞间通讯中的可能功能应该得到解决。
miR-375 is a highly abundant miRNA in Merkel cell carcinoma (MCC). In other cancers, it acts as either a tumor suppressor or oncogene. While free-circulating miR-375 serves as a surrogate marker for tumor burden in patients with advanced MCC, its function within MCC cells has not been established. Nearly complete miR-375 knockdown in MCC cell lines was achieved using antagomiRs via nucleofection. The cell viability, growth characteristics, and morphology were not altered by this knockdown. miR-375 target genes and related signaling pathways were determined using Encyclopedia of RNA Interactomes (ENCORI) revealing Hippo signaling and epithelial to mesenchymal transition (EMT)-related genes likely to be regulated. Therefore, their expression was analyzed by multiplexed qRT-PCR after miR-375 knockdown, demonstrating only a limited change in expression. In summary, highly effective miR-375 knockdown in classical MCC cell lines did not significantly change the cell viability, morphology, or oncogenic signaling pathways. These observations render miR-375 an unlikely intracellular oncogene in MCC cells, thus suggesting that likely functions of miR-375 for the intercellular communication of MCC should be addressed.