MiR-340 affects gastric cancer cell proliferation, cycle, and apoptosis through regulating SOCS3/JAK-STAT signaling

Chunhong Xiao1, Hong Hong1, Haizhong Yu1

  • 1a Department of Clinical Laboratory , Nantong Tumor Hospital , Nantong , Jiangsu , China.

Abstract

Insights

MicroRNA-340 (miR-340) suppresses gastric cancer (GC) progression by targeting Suppressors of Cytokine Signaling 3 (SOCS3). Downregulating miR-340 increases SOCS3, inhibiting the Janus kinase (JAK)-STAT3 pathway, thus reducing GC cell proliferation and promoting apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is implicated in tumorigenesis.
  • Suppressors of Cytokine Signaling 3 (SOCS3) acts as a negative regulator of the JAK-STAT signaling pathway.
  • MicroRNA-340 (miR-340) is upregulated in gastric cancer (GC) tissues.

Purpose of the Study:

  • To investigate the role of miR-340 in regulating SOCS3 expression in gastric cancer.
  • To determine the effect of miR-340 on GC cell proliferation, cell cycle, and apoptosis.
  • To elucidate the underlying molecular mechanisms involving the JAK-STAT3 signaling pathway.

Main Methods:

  • Bioinformatics analysis and dual luciferase assays were employed to confirm the targeting relationship between miR-340 and SOCS3 mRNA.
  • Expression levels of miR-340, SOCS3, p-JAK, p-STAT3, and Survivin were compared between GC and normal tissues, and between GC and normal cell lines (MKN-28 and GES-1).
  • In vitro experiments involved transfecting MKN-28 cells with anti-miR-340 or pSicoR-SOCS3, followed by assessments of cell proliferation, cell cycle, and apoptosis using flow cytometry.

Main Results:

  • A direct targeting relationship between miR-340 and the 3'-UTR of SOCS3 mRNA was identified.
  • GC tissues and cells exhibited significantly elevated miR-340 levels and reduced SOCS3 expression compared to normal controls.
  • Downregulation of miR-340 led to increased SOCS3 expression, suppressed JAK-STAT3 signaling (reduced p-JAK, p-STAT3, Survivin), attenuated proliferation, cell cycle arrest, and enhanced apoptosis in GC cells.

Conclusions:

  • MiR-340 plays a crucial role in gastric cancer progression.
  • Upregulation of SOCS3 by miR-340 downregulation inhibits the JAK-STAT3 signaling pathway.
  • Targeting miR-340 presents a potential therapeutic strategy for gastric cancer by inhibiting proliferation and promoting apoptosis.

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