Department of Oral Science, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Int J Mol Sci. 2021 Sep 14;22(18):9947. doi: 10.3390/ijms22189947.
We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including (the guide strand) and (the passenger strand) of , were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre- ( and ) in HNSCC cells. Of these, the (guanine nucleotide-binding protein subunit alpha-12) and (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses ( = 0.0018 and = 0.0104, respectively). Direct regulation of and by in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of and was detected in clinical specimens of HNSCC through immunostaining. The involvement of (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC.
我们新生成了一个基于 RNA 测序的头颈部鳞状细胞癌（HNSCC）microRNA（miRNA）表达特征。该特征的分析表明，包括在内的一些 miRNA 的两条链（指导链）和（过客链）在 HNSCC 组织中下调。对癌症基因组图谱的分析证实了在 HNSCC 中低表达。这些 miRNA 的异位表达减弱了癌细胞侵袭性的特征（例如细胞增殖、迁移和侵袭）。我们的计算机分析总共揭示了 28 个在 HNSCC 细胞中受前体（和）调节的假定靶标。其中，和（鸟嘌呤核苷酸结合蛋白亚基α-12）和（氧化型低密度脂蛋白受体 1）的表达水平被确定为根据多变量 Cox 回归分析预测患者生存的独立因素（=0.0018 和=0.0104，分别）。通过荧光素酶报告基因检测证实了在 HNSCC 细胞中对和的直接调控。此外，通过免疫染色在 HNSCC 的临床标本中检测到和的过表达。在 HNSCC 的肿瘤发生中涉及到（过客链）是癌症生物学中的一个新概念。我们基于 miRNA 的策略将增加对头颈部鳞状细胞癌分子发病机制的认识。
