Int J Mol Med . 2016 Jul;38(1):113-22. doi: 10.3892/ijmm.2016.2619. Epub 2016 May 31.

miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression

Sen Jiang  1 Chao Zhao  1 Xiaodi Yang  2 Xiangyang Li  1 Qing Pan  3 Haijin Huang  1 Xuyang Wen  1 Husheng Shan  1 Qianwen Li  1 Yunxiang Du  1 Yaping Zhao  1

Affiliations

  • 1 The 82nd Hospital of the People’s Liberation Army, Huaian, Jiangsu 223001, P.R. China.
  • 2 Department of Gastroenterology, Shanghai Sixth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, P.R. China.
  • 3 Department of Laboratory Medicine, Huaiyin Hospital of Huaian city, Huaian, Jiangsu 233004, P.R. China.

Abstract

Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR‑1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR‑1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR‑1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR‑1 promoted cell proliferation and decreased apoptosis, suggesting that miR‑1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR‑1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR‑1. miR‑1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR‑1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR‑1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC.

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