miR-550a-3/NFIC plays a driving role in esophageal squamous cell cancer cells proliferation and metastasis partly through EMT process

Mol Cell Biochem. 2020 Sep;472(1-2):115-123. doi: 10.1007/s11010-020-03790-y. Epub 2020 Jun 21.

Abstract

In this study, the functional role of miR-550a-3 and its direct target nuclear factor IC (NFIC) in esophageal squamous cell cancer (ESCC) cells were explored. Differential expression of miR-550a-3 in ESCC tissues was acquired from TCGA database, and Kaplan-Meier method was used to determine the relationship between miR-550a-3 expression and survival time of ESCC patients. Expression level of miR-550a-3 in several ESCC cell lines was measured by qRT-PCR. Two cell lines including Eca109 and JAR were used to perform proliferation, cloning, invasion and migration experiments. Targeted relationship between miR-550a-3 and NFIC was speculated by predication software and confirmed by dual luciferase assay. Additionally, potential relationship between miR-550a-3 and NFIC was analyzed by Spearman rank correlation analysis and western blot. Rescue assays were performed to explore the function of miR-550a-3/NFIC in ESCC cells biological behaviors. Expression levels of key proteins involved in epithelial-to-mesenchymal transition (EMT) process were determined by western blot. By consulting TCGA database, we found that high expression of miR-550a-3 was positively connected with the poor prognosis of patients with ESCC. In addition, overexpression of miR-550a-3 promoted the proliferation, colony formation and metastasis of ESCC cells. Moreover, rescue assays revealed that overexpression of NFIC attenuated the promoting effects of miR-550a-3 on ESCC cells malignant behaviors. While the promoting effects of miR-550a-3 on EMT process were inhibited by NFIC. Our results illustrate the importance of miR-550a-3/NFIC in regulation of ESCC cells growth and metastasis, which could contribute to developing novel target for early diagnosis or neoteric therapeutic target for ESCC.

Keywords: Aggressiveness; Esophageal squamous cell cancer; NFIC; Proliferation; miR-550a-3.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • NFI Transcription Factors / genetics
  • NFI Transcription Factors / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • MIRN550 microRNA, human
  • MicroRNAs
  • NFI Transcription Factors
  • NFIC protein, human