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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-330-3p inhibits gastric cancer progression through targeting MSI1
Aoran Guan1, Hui Wang2, Xun Li1
1Department of General Surgery, The Affiliated Yan an Hospital of Kunming Medical University Kunming 650051, Yunnan, China.
Abstract:
Increasing evidences demonstrated that microRNAs (miRNAs) play critical roles in the human tumor development and progression. In our study, we found that miR-330-3p expression was downregulated in gastric cancer cell lines and tissues. Ectopic expression of miR-330-3p suppressed the gastric cancer cell proliferation, colony formation and migration. Overexpression of miR-330-3p promoted E-cadherin expression and inhibited the expression of N-cadherin, vimentin and snail. We identified Musashi-1 (MSI1) as a direct target gene of miR-330-3p in gastric cancer cell. In addition, MSI1 was upregulated in gastric cancer cell lines and tissues and the MSI1 expression was inversely correlated with miR-330-3p expression in gastric cancer tissues. MiR-330-3p expression was increased in gastric cancer cells after treated with histone deacetylase inhibitor trichostatin A (TSA) and DNA methylation inhibitor 5-aza-CdR (AZA). These indicated that downregulated expression of miR-330-3p was partly mediated by gene promoter region hypermethylation. These results suggested that miR-330-3p acted as a tumor suppressor gene in GC.
Insights
MicroRNA-330-3p (miR-330-3p) is downregulated in gastric cancer, acting as a tumor suppressor. Restoring miR-330-3p inhibits cancer cell growth and migration by targeting Musashi-1.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators in tumor development.
- Gastric cancer (GC) progression involves complex molecular alterations.
- Understanding miRNA roles in GC is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the role of miR-330-3p in gastric cancer.
- To identify the target genes and regulatory mechanisms of miR-330-3p in GC.
- To evaluate miR-330-3p as a potential tumor suppressor in GC.
Main Methods:
- Quantitative real-time PCR to assess miR-330-3p and MSI1 expression in GC cell lines and tissues.
- Cell proliferation, colony formation, and migration assays.
- Western blotting to analyze protein expression (E-cadherin, N-cadherin, vimentin, snail).
- Luciferase reporter assays to confirm direct targeting of MSI1 by miR-330-3p.
- Treatment with epigenetic modifiers (TSA, AZA) to investigate miR-330-3p regulation.
Main Results:
- miR-330-3p expression was significantly downregulated in gastric cancer tissues and cell lines.
- Overexpression of miR-330-3p suppressed gastric cancer cell proliferation, colony formation, and migration.
- miR-330-3p overexpression promoted E-cadherin and inhibited N-cadherin, vimentin, and snail expression.
- Musashi-1 (MSI1) was identified as a direct target of miR-330-3p and was upregulated in GC.
- MSI1 expression was inversely correlated with miR-330-3p levels in GC tissues.
- miR-330-3p expression increased upon treatment with TSA and AZA, suggesting epigenetic regulation via hypermethylation.
Conclusions:
- miR-330-3p functions as a tumor suppressor gene in gastric cancer.
- Downregulation of miR-330-3p in GC is partly mediated by epigenetic silencing.
- Targeting the miR-330-3p/MSI1 axis may offer a therapeutic strategy for gastric cancer.
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