Hypoxic miRNAs expression are different between primary and metastatic melanoma cells

Hypoxic miRNAs expression are different between primary and metastatic melanoma cells
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DOI：
10.1016/j.gene.2021.145552
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发表时间：
2021-03-18
期刊：
GENE
影响因子：
3.5
通讯作者：
Miura, Naoki
Miura, Naoki
中科院分区：
生物学3区
文献类型：
--
作者：
Hino, Yasunori;Rahman, Md Mahfuzur;Miura, Naoki

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MicroRNA (miRNA) 可以快速响应细胞应激，例如缺氧。这种即时的 miRNA 反应可调节众多基因并影响多种信号传导途径。因此，鉴定缺氧调节的 miRNA（HRM）对于犬口腔黑色素瘤（COM）研究其临床意义非常重要。通过二代测序研究了两种 COM 细胞系的低氧和常氧 miRNA 谱。通过比较这些细胞系与 COM 组织中的 miRNA 表达谱来鉴定 HRM。除 miR-301a 和 miR-8884 外，原发性和转移性来源的细胞系之间的 HRM 谱不同。通过 qRT-PCR 测定的 miRNA 表达的时间进程，尤其是 miR-210 和 miR-301a，表明转移细胞比原代细胞更能抵抗缺氧。对经过实验验证的人类 miRNA 靶数据库的分析表明，miR-21 和 miR-301a 控制着一个复杂的基因调控网络以应对缺氧，其中包括众所周知的癌基因的通路，例如 VEGF、PTEN 和 TGFBR2。总之，我们揭示了COM的HRM。此外，我们的研究表明原发性黑色素瘤细胞和转移性黑色素瘤细胞之间缺氧 miRNA 的调节和反应存在差异。
MicroRNAs (miRNAs) can rapidly respond to cellular stresses, such as hypoxia. This immediate miRNA response regulates numerous genes and influences multiple signaling pathways. Therefore, identifying hypoxia-regulated miRNAs (HRMs) is important in canine oral melanoma (COM) to investigate their clinical significance. The hypoxic and normoxic miRNA profiles of two COM cell lines were investigated by next generation sequencing. HRMs were identified by comparing miRNA expression profiles in these cell lines with that in COM tissue. The HRM profile was different between cell lines of primary and metastatic origin, except for miR-301a and miR-8884. The time course of miRNA expression determined by qRT-PCR, especially for miR-210 and miR-301a, showed that metastatic cells are more resistant to hypoxia than primary cells. Analysis of an experimentally validated human miRNA target database revealed that miR-21 and miR-301a control a complex gene regulatory network in response to hypoxia, which includes pathways of well-known oncogenes, such as VEGF, PTEN, and TGFBR2. In conclusions, we revealed the HRM of COM. Moreover, our study shows the difference in regulation and response of hypoxic miRNAs between primary and metastatic originated melanoma cells.