MicroRNA-143-3p suppresses cell growth and invasion in laryngeal squamous cell carcinoma via targeting the k-Ras/Raf/MEK/ERK signaling pathway

Abstract

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.