MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathwayResearch in context
Wei-Wei Wang,
Zhi-Hua Zhao,
Li Wang,
Pan Li,
Kui-Sheng Chen,
Jian-Ying Zhang,
Wen-Cai Li,
Guo-Zhong Jiang,
Xiang-Nan Li
Affiliations
Wei-Wei Wang
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China
Zhi-Hua Zhao
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China
Li Wang
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China
Pan Li
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China
Kui-Sheng Chen
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China
Jian-Ying Zhang
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
Wen-Cai Li
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China; Correspondence to: W.-C. Li and G.-Z. Jiang, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou 450052, Henan Province, China.
Guo-Zhong Jiang
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pathology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450002, China; Henan Key Laboratory for Tumor Pathology, Zhengzhou 450052, China; Correspondence to: W.-C. Li and G.-Z. Jiang, Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou 450052, Henan Province, China.
Xiang-Nan Li
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Correspondence to: X.-N. Li, Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou 450052, Henan Province, China.
Background: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. Methods: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. Findings: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. Interpretation: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC. Keywords: microRNA-134, PLXNA1, MAPK signalling pathway, Esophageal squamous cell carcinoma, Proliferation, Apoptosis, Lymph node metastasis
