Zhen Cai1, Xiu-Yan Hao1, Feng-Xin Liu2. 1. Department of Oral and Maxillofacial Surgery, Linyi People's Hospital, Linyi, Shandong, 276003, China. 2. Department of Oral and Maxillofacial Surgery, Linyi People's Hospital, Linyi, Shandong, 276003, China. Electronic address: liufengxin25@yeah.net.
Abstract
OBJECTIVE: MicroRNAs (miRs) have been shown to play critical roles in the pathogenesis of oral squamous cell carcinoma (OSCC), the current study is designed to identify the potential role of miR-186 in OSCC. MATERIALS AND METHODS: Realtime polymerase chain reaction was used to determine miR-186 expression in paired tissue samples (OSCC and adjacent normal tissues) and multiple oral cell lines (normal oral keratinocyte HOK cell and OSCC cell lines). Cell viability, colony formation and flow cytometry assays were used to assess the biological function of miR-186. Furthermore, luciferase and western blot assays were used to verify the predicted target of miR-186. RESULTS: We found that miR-186 expression was significantly downregulated in OSCC tissues and cell lines. Overexpression of miR-186 produced an anti-growth effect and induced apoptosis in Tca8113 and SCC-25 cells. Luciferase assay revealed that miR-186 directly targeted PTPN11 (a gene encodes the protein tyrosine phosphatase SHP2) mRNA 3' untranslated region and suppressed its expression. Consistently, MiR-186 and SHP2 were negatively correlated in OSCC tissues. Consequently, miR-186 inhibited signaling activities of Extracellular Regulated protein Kinases (ERK) and Protein kinase B (AKT), which act downstream of SHP2 and are critical for growth of cancer cells. CONCLUSION: We identify that miR-186 serves as a tumor suppressor in OSCC. Downregulation of this microRNA may lead to a higher expression of oncogenic factor SHP2, which leads to activation of growth promoting signaling. Thus, miR-186 may be a novel and effective therapeutic agent for the treatment of OSCC.
OBJECTIVE: MicroRNAs (miRs) have been shown to play critical roles in the pathogenesis of oral squamous cell carcinoma (OSCC), the current study is designed to identify the potential role of miR-186 in OSCC. MATERIALS AND METHODS: Realtime polymerase chain reaction was used to determine miR-186 expression in paired tissue samples (OSCC and adjacent normal tissues) and multiple oral cell lines (normal oral keratinocyte HOK cell and OSCC cell lines). Cell viability, colony formation and flow cytometry assays were used to assess the biological function of miR-186. Furthermore, luciferase and western blot assays were used to verify the predicted target of miR-186. RESULTS: We found that miR-186 expression was significantly downregulated in OSCC tissues and cell lines. Overexpression of miR-186 produced an anti-growth effect and induced apoptosis in Tca8113 and SCC-25 cells. Luciferase assay revealed that miR-186 directly targeted PTPN11 (a gene encodes the protein tyrosine phosphatase SHP2) mRNA 3' untranslated region and suppressed its expression. Consistently, MiR-186 and SHP2 were negatively correlated in OSCC tissues. Consequently, miR-186 inhibited signaling activities of Extracellular Regulated protein Kinases (ERK) and Protein kinase B (AKT), which act downstream of SHP2 and are critical for growth of cancer cells. CONCLUSION: We identify that miR-186 serves as a tumor suppressor in OSCC. Downregulation of this microRNA may lead to a higher expression of oncogenic factor SHP2, which leads to activation of growth promoting signaling. Thus, miR-186 may be a novel and effective therapeutic agent for the treatment of OSCC.
Authors: Sang Shin Lee; Jong Ho Choi; Seung Mook Lim; Gi Jin Kim; Suk Keun Lee; Yoon Kyung Jeon Journal: Int J Mol Sci Date: 2021-01-20 Impact factor: 5.923