miR-618 Suppresses Metastasis in Gastric Cancer by Downregulating the Expression of TGF-β2

Anat Rec (Hoboken). 2019 Jun;302(6):931-940. doi: 10.1002/ar.24083. Epub 2019 Feb 25.

Abstract

Recent studies have demonstrated that microRNAs regulate gene expression and are related to cancer progression. Increasing evidence shows that miR-618 plays an important role in a variety of tumors, including thyroid carcinomas, breast cancer and lymphoma cancer. However, no studies have examined the expression or function of miR-618 in gastric cancer (GC). In this study, we examined the effects and molecular mechanisms of miR-618 in GC. We compared the expression levels of miR-618 in 90 paired GC tissues and adjacent noncancerous tissues. Cell cycle, apoptosis and transwell assays were performed in GC cells with miR-618 mimic or inhibitor in vitro. We first used quantitative PCR(qPCR) to show that miR-618 expression levels were downregulated in GC tissues, which showed statistical significance. Next we used transwell assays to prove that miR-618 suppressed the invasion and migration capacity of GC cells. Furthermore, screening of the miRDB and Target Scan Human databases indicated TGF-β2 as a downstream target of miR-618. In further research, we identified TGF-β2 as a target gene of miR-618 by the luciferase reporter assay. Western blot analysis confirmed that TGF-β2 expression was inversely correlated with miR-618 expression. In situ hybridization showed that miR-618 expression level was downregulated in GC tissues. In conclusion, our findings suggest that miR-618 may function as a tumor suppressor in GC and suppresses metastasis in GC by negatively regulating the transcriptional level of TGF-β2. Anat Rec, 302:931-940, 2019. © 2019 Wiley Periodicals, Inc.

Keywords: TGF-β2; gastric cancer; miR-618.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor*
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Signal Transduction / genetics
  • Stomach / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transforming Growth Factor beta2 / genetics*

Substances

  • MIRN618 microRNA, human
  • MicroRNAs
  • TGFB2 protein, human
  • Transforming Growth Factor beta2