Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma

Exp Cell Res. 2016 Nov 1;348(2):146-154. doi: 10.1016/j.yexcr.2016.09.010. Epub 2016 Sep 19.

Abstract

Purpose: This study aims to examine the expression profiles miR-1288 in oesophageal squamous cell carcinoma (ESCC). The cellular implications and target interactions of ESCC cells following miR-1288 overexpression was also examined.

Methods: In total, 120 oesophageal tissues (90 primary ESCCs and 30 non-neoplastic tissues) were recruited for miR-1288 expression analysis using qRT-PCR. An exogenous miR-1288 mimic and its inhibitor were used to explore the in-vitro effects of miR-1288 on ESCC cells by performing cell proliferation, colony formation, cell invasion and migration assays. Localisation and modulatory changes of various miR-1288 regulated proteins such as FOXO1, p53, TAB3, BCL2 and kRAS was examined using immunofluorescence and western blot.

Results: Overexpression of miR-1288 was more often noted in ESCC tissues when compared to non-neoplastic oesophageal tissues. High expression was often noted in high grade carcinomas and with metastases. Patients with high levels of miR-1288 expression showed a slightly better survival compared to patients with low miR-1288 levels. Furthermore, overexpression of miR-1288 showed increased cell proliferation and colony formation, improved cell migration and enhanced cell invasion properties in ESCC cells. In addition, miR-1288 overexpression in ESCC cells showed repression of cytoplasmic tumour suppressor FOXO1 protein expression. Inversely, inhibition of miR-1288 expression exhibited remarkable upregulation of FOXO1 protein, while expressions of other tested proteins remain unchanged.

Conclusions: Up regulation of miR-1288 expression in ESCC tissues and miR-1288 induced oncogenic features of ESCC cells in-vitro indicates the oncogenic roles of miR-1288 in ESCCs. Overexpression of miR-1288 play a key role in the pathogenesis of ESCCs and its modulation may have potential therapeutic value in patients with ESCC.

Keywords: FOXO1; Oesophageal; Squamous cell carcinoma; miR-1288.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basement Membrane / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Extracts
  • Cell Line, Tumor
  • Cell Proliferation
  • Clone Cells
  • Down-Regulation / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Fluorescent Antibody Technique
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Reproducibility of Results
  • Survival Analysis
  • Transfection
  • Tumor Stem Cell Assay

Substances

  • Cell Extracts
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • MIRN1288 microRNA, human
  • MicroRNAs