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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-508-5p suppresses metastasis in human gastric cancer by targeting S-phase kinase‑associated protein 2
Xiangguo Duan1, Jing Bai2, Jun Wei1
1Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
Abstract:
S-phase kinase-associated protein 2 (SKP2), a potent oncogene was revealed to be upregulated in gastric cancer (GC) tissue samples, in which SKP2 was inversely correlated with microRNA (miR)‑508‑5p transcripts. In present study, the functional effect of miR‑508‑5p on SKP2 and its metastatic potential were investigated in SGC‑7901 GC cells. Significant downregulation of the miR‑508‑5p transcript was associated with the progression of GC. Furthermore, the overexpression of miR‑508‑5p was demonstrated to inhibit the proliferation, migration and invasion of SGC‑7901 cells, as well as induced cell apoptosis and cell cycle arrest at the G0/G1 phase in vitro. The overexpression of miR‑508‑5p was able to downregulate the expression of the SKP2 oncogene, through a mechanism by which miR‑508‑5p directly targeted the SKP2 gene. Thus, regulating transcriptional and post‑transcriptional SKP2 expression, as demonstrated using luciferase reporter assays, reverse transcription‑quantitative polymerase chain reaction analysis and immunoblotting assays. The results of the present study identified that miR‑508‑5p functionally affects the SKP2 gene and reduces metastatic potential in GC, suggesting a novel role of miR‑508‑5p in the regulation of SKP2 and cell cycle.
Insights
MicroRNA-508-5p suppresses gastric cancer (GC) progression by targeting the S-phase kinase-associated protein 2 (SKP2) oncogene. This microRNA inhibits cell proliferation, migration, and invasion, offering a potential therapeutic target for GC.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- S-phase kinase-associated protein 2 (SKP2) is a significant oncogene frequently upregulated in gastric cancer (GC).
- SKP2 upregulation in GC tissues shows an inverse correlation with microRNA (miR)‑508‑5p transcript levels.
- Downregulation of miR‑508‑5p is associated with GC progression.
Purpose of the Study:
- To investigate the functional impact of miR‑508‑5p on SKP2 expression and its role in gastric cancer cell metastasis.
- To elucidate the mechanism by which miR‑508‑5p affects SKP2 and cellular processes in SGC‑7901 GC cells.
Main Methods:
- Overexpression of miR‑508‑5p in SGC‑7901 GC cells.
- Assays conducted: luciferase reporter assays, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and immunoblotting.
- Evaluation of cell proliferation, migration, invasion, apoptosis, and cell cycle distribution.
Main Results:
- Overexpression of miR‑508‑5p significantly inhibited proliferation, migration, and invasion of SGC‑7901 cells.
- miR‑508‑5p induced apoptosis and cell cycle arrest at the G0/G1 phase.
- miR‑508‑5p directly targets the SKP2 gene, downregulating its transcriptional and post-transcriptional expression.
Conclusions:
- miR‑508‑5p plays a crucial role in suppressing gastric cancer progression and metastasis by targeting the SKP2 oncogene.
- The findings suggest miR‑508‑5p as a potential therapeutic agent for gastric cancer.
- miR‑508‑5p regulates SKP2 expression and impacts cell cycle control in gastric cancer.
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