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

Abstract

Objective: Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway is closely related to tumorigenesis. Suppressors of cytokine signaling 3 (SOCS3) is a negative regulator of JAK-STAT signaling pathway. MiR-340 expression is significantly upregulated in gastric cancer (GC) tissue. This study investigated the role of miR-340 in regulating SOCS3 expression and affecting GC cell proliferation, cycle, and apoptosis.

Patients and methods: Dual luciferase assay was used to verify the targeted relationship between miR-340 and SOCS3. GC tissue was collected from patients. Normal gastric mucosal tissue was selected as control. MiR-340, SOCS3, p-JAK, p-STAT3, and Survivin protein expressions were compared with GES-1 and MKN-28 cells. MKN-28 cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-340, pSicoR-Blank, and pSicoR-SOCS3 groups. Cell proliferation, cycle, and apoptosis were detected by flow cytometry.

Results: Bioinformatics analysis revealed the targeted relationship between miR-340 and the 3′-UTR of SOCS3 mRNA. Dual luciferase assay demonstrated that miR-340 regulated SOCS3 expression. MiR-340 level was significantly elevated, while SOCS3 level was obviously declined in GC tissue compared with normal mucosal tissue. MiR-340, p-JAK, p-STAT3, and Survivin expressions were upregulated, whereas SOCS3 expression was reduced in MKN-28 cells compared with that in GES-1 cells. Anti-miR-340 or pSicoR-SOCS3 transfection markedly increased SOCS3 expression, reduced p-JAK, p-STAT3, and Survivin levels, attenuated cell proliferation, arrested cell cycle, and enhanced cell apoptosis in MKN-28 cells.

Conclusions: Downregulation of miR-340 inhibited GC cell proliferation, arrested cell cycle, and facilitated apoptosis through upregulating SOCS3 expression to suppress JAK-STAT3 signaling pathway.

Keywords:

• miR-340
• SOCS3
• JAK-STAT3
• gastric cancer
• proliferation
• cell cycle
• apoptosis

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Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Nantong Municipal Science and technology plan project number [MS22016061].