Ear Nose and Throat Hospital, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Int J Oncol. 2019 Feb;54(2):689-701. doi: 10.3892/ijo.2018.4655. Epub 2018 Dec 6.
MicroRNAs (miRNAs or miRs) have been identified as an important regulator in carcinogenesis and other pathological processes. However, the molecular mechanism underlying the function of miRNAs in the progression and development of laryngeal squamous cell carcinoma (LSCC) remains to be fully elucidated. In the present study, the miRNA expression pattern in LSCC tissues was profiled using miRNA microarray analysis. It was found that a large set of miRNAs are aberrantly expressed in LSCC tissues and that miR‑143‑3p was the most markedly downregulated compared with normal tissues. The low expression of miR‑143‑3p was associated with poor prognosis in LSCC. The overexpression of miR‑143‑3p repressed cellular proliferation and induced apoptosis in vitro, and inhibited tumor growth in vivo. The upregulation of miR‑143‑3p suppressed cell migration and invasion through inhibiting the epithelial‑mesenchymal transition cascade. In addition, it was verified that the oncogene k‑Ras is a target of miR‑143‑3p in LSCC cells, and the suppressive effects of miR‑143‑3p on LSCC cells were abrogated by the overexpression of k‑Ras. It was also revealed that miR‑143‑3p may inhibit cell growth and metastasis through targeting the k‑Ras/Raf/mitogen‑activated protein kinase kinase (MEK)/extracellular signal‑regulated kinase (ERK) signaling pathway. Taken together, the data indicated that the miR‑143‑3p/k‑Ras/Raf/MEK/ERK axis serves a key regulator in the development and progression of LSCC, suggesting that miR‑143‑3p may be a potential prognostic biomarker and therapeutic target in the treatment of LSCC.
微小 RNA(miRNAs 或 miRs)已被鉴定为癌发生和其他病理过程中的重要调节剂。然而,miRNAs 在喉鳞状细胞癌(LSCC)进展和发展中的功能的分子机制仍有待充分阐明。在本研究中,使用 miRNA 微阵列分析对 LSCC 组织中的 miRNA 表达模式进行了分析。结果发现,与正常组织相比,LSCC 组织中存在大量异常表达的 miRNAs,miR-143-3p 的表达下调最为显著。miR-143-3p 的低表达与 LSCC 的不良预后相关。miR-143-3p 的过表达在体外抑制细胞增殖并诱导细胞凋亡,并在体内抑制肿瘤生长。miR-143-3p 的上调通过抑制上皮-间充质转化级联反应抑制细胞迁移和侵袭。此外,验证了 k-Ras 是 LSCC 细胞中 miR-143-3p 的靶基因,并且通过过表达 k-Ras 可以消除 miR-143-3p 对 LSCC 细胞的抑制作用。还表明,miR-143-3p 可能通过靶向 k-Ras/Raf/丝裂原激活蛋白激酶激酶(MEK)/细胞外信号调节激酶(ERK)信号通路抑制细胞生长和转移。综上所述,数据表明 miR-143-3p/k-Ras/Raf/MEK/ERK 轴在 LSCC 的发展和进展中起关键调节作用,表明 miR-143-3p 可能是 LSCC 治疗中潜在的预后生物标志物和治疗靶标。