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Published on: September 1, 2019
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.
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.
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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