MicroRNA‑4284 promotes gastric cancer tumorigenicity by targeting ten-eleven translocation 1

Mol Med Rep. 2018 May;17(5):6569-6575. doi: 10.3892/mmr.2018.8671. Epub 2018 Mar 1.

Abstract

Increasing evidence has shown that abnormal expression of miR-4284 participates in the progression of several types of cancer. However, the expression and the role of miR‑4284 in gastric cancer remain largely unknown. Therefore, in the present study the miR‑4284 expression levels in gastric cancer tissues and cell lines, was examined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and found that miR‑4284 was significantly upregulated in 40 pairs of gastric cancer tissues and five gastric cancer cell lines compared to the corresponding normal tissues and GES‑1 cell line. In addition, increased miR‑4284 expression was positively associated with TNM stage (P=0.035), distal metastasis (P=0.022) and poor prognosis in gastric cancer patients. Furthermore, the overexpression of miR‑4284 expression was shown to promote cell proliferation, clone formation, invasion and migration, while the suppression of miR‑4284 expression induced opposite effects. Additionally, luciferase reporter assay was conducted and showed that ten-eleven translocation 1 (TET1), a tumor suppressor gene that regulating cell survival and metastasis, was a direct target of miR‑4284. Upregulated miR‑4284 decreased the mRNA and protein levels of TET1 in SGC‑7901 cells and downregulated miR‑4284 increased the mRNA and protein levels of TET1 in AGS cells. In addition, miR‑4284 expression was negatively correlated with the TET1 expression in gastric cancer tissues. Moreover, inhibition of TET1 suppressed the effect of miR‑4284 inhibitors on cell proliferation in AGS cells. Therefore, data demonstrated that miR‑4284 could promote tumor cell growth, migration and invasion by directly targeting TET1 in gastric cancer, which may provide a potential therapeutic target for gastric cancer treatment.

Keywords: cell migration; gastric cancer; miR-4284; prognosis; TET1.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Cell Survival
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mixed Function Oxygenases / biosynthesis*
  • Mixed Function Oxygenases / genetics
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • MIRN4284 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Neoplasm
  • Mixed Function Oxygenases
  • TET1 protein, human