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.

Impact of K-Ras Over-expression in Laryngeal Squamous Cell Carcinoma

“…Similarly, microRNA (miR) analysis in LSCC based on specific markers such as miR-143-3p seems to add critical molecular information regarding the K-Ras expression patterns in them. A study group suggested that enhanced miR-143-3p inhibited cell growth and metastasis suppressing the K-Ras/Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signalling pathway (17). Co-analyzing epidermal growth factor receptor (EGFR) and K-Ras genes by applying high resolution melting analysis (HRMA) and one-step real-time polymerase chain reaction (PCR), a study group reported a very limited K-Ras mutational rate in the Belgian population with Head and Neck Squamous Cell Carcinoma (HNSCC) including LSCC cases (7% of the specimens, only one case with point mutation) (18).…”

miR‑375‑3p inhibits the progression of laryngeal squamous cell carcinoma by targeting hepatocyte nuclear factor‑1β

“…The prognosis and treatment of LSCC have improved with advancements in therapeutic strategies; the 5-year overall survival rate of patients with LSCC is ~64% ( 5 ). Increasing evidence suggest that miRNAs exert tumor suppressive or oncogenic functions in the progression of LSCC ( 21 , 40 – 42 ). A previous study reported that miR-375-3p is downregulated in head and neck cancer ( 24 ).…”

Effects of MIR143 on rat sarcoma signaling networks in solid tumors: A brief overview

“…Zhang et al 57 reported that MIR143‐3p exhibits an anti–tumor effect on laryngeal squamous cell carcinoma, the most frequent cancer of the head and neck cancers, by targeting KRAS and its effector MAPK/ERK signaling pathway. In addition, Xu’s group demonstrated that the MIR143 overexpression inhibits the cell growth of nasopharyngeal cancer both in vitro and in vivo 58 .…”