Impact of miR-1/miR-133 Clustered miRNAs: PFN2 Facilitates Malignant Phenotypes in Head and Neck Squamous Cell Carcinoma.

Impact of miR-1/miR-133 Clustered miRNAs: PFN2 Facilitates Malignant Phenotypes in Head and Neck Squamous Cell Carcinoma.
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DOI:
10.3390/biomedicines10030663
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发表时间:
2022-03-12
期刊:
影响因子:
4.7
通讯作者:
Seki N
Seki N
中科院分区:
工程技术3区
文献类型:
--
作者:
Asai S;Koma A;Nohata N;Kinoshita T;Kikkawa N;Kato M;Minemura C;Uzawa K;Hanazawa T;Seki N

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基于我们最初的基于RNA序列的头颈部鳞状细胞癌(HNSCC)的microRNA(miRNA)特征,揭示了miR-1- 3 p、miR-206、miR-133 a-3 p和miR-133 b的表达水平在癌症标本中被显著抑制。miR-1- 3 p/miR-206和miR-133 a-3 p/miR-133 b的种子序列相同。有趣的是,miR-1- 3 p/miR-133 a-3 p和miR-206/miR-133 b在人类基因组中聚集。我们推测这些miRNAs协同调控的基因与HNSCC的恶性转化密切相关。我们的计算机分析鉴定了总共28个具有推定的miR-1- 3 p/miR-133 a-3 p和miR-206/miR-133 b结合位点的基因。此外,它们的表达水平在HNSCC组织中上调。多因素考克斯回归分析显示PFN 2和PSEN 1的表达是影响HNSCC患者预后的独立因素(p < 0.05)。值得注意的是,四种miRNA(即,miR-1- 3 p、miR-206、miR-133 a-3 p和miR-133 b)直接结合PFN 2的3′非翻译区并控制该基因在HNSCC细胞中的表达。PFN 2的过表达在临床标本中得到证实,其异常表达促进癌细胞的迁移和侵袭能力。我们基于miRNA的策略继续发现与HNSCC肿瘤发生密切相关的新基因。
Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p/miR-206 and miR-133a-3p/miR-133b are identical. Interestingly, miR-1-3p/miR-133a-3p and miR-206/miR-133b are clustered in the human genome. We hypothesized that the genes coordinately controlled by these miRNAs are closely involved in the malignant transformation of HNSCC. Our in silico analysis identified a total of 28 genes that had putative miR-1-3p/miR-133a-3p and miR-206/miR-133b binding sites. Moreover, their expression levels were upregulated in HNSCC tissues. Multivariate Cox regression analyses showed that expression of PFN2 and PSEN1 were independent prognostic factors for patients with HNSCC (p < 0.05). Notably, four miRNAs (i.e., miR-1-3p, miR-206, miR-133a-3p, and miR-133b) directly bound the 3′untranslated region of PFN2 and controlled expression of the gene in HNSCC cells. Overexpression of PFN2 was confirmed in clinical specimens, and its aberrant expression facilitated cancer cell migration and invasion abilities. Our miRNA-based strategy continues to uncover novel genes closely involved in the oncogenesis of HNSCC.
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