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Published on: September 15, 2023
miR-429 modulates the expression of c-myc in human gastric carcinoma cells
Tiewei Sun1, Chunmei Wang, Jun Xing
1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Hei LongJiang, Harbin, China.
Aim:
MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression and may contribute to the development and progression of many cancers. In this study, our goal was to investigate the regulation of miR-429 in gastric cancer and explored the mechanism/s by which it influenced pathogenesis of gastric cancer.
Methods:
We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression level of miR-429 in 52 gastric cancer tissues and their paracancerous tissues. Bioinformatics was used to predict downstream target genes of miR-429. SGC-7901 gastric cancer cells were transfected with miR-429 mimics and endogenous c-myc expression was detected by western blots. We performed functional assays using the 3'UTR of the c-myc gene as a miR-429 target in a luciferase reporter assay system.
Results:
We showed that miR-429 was downregulated in human gastric carcinoma tissue and in SGC-7901 cells. Cell viability, proliferation and attachment were inhibited in miR-429-transfected cells. miR-429 significantly downregulated endogenous c-myc expression in SGC-7901 cells. Action of miR/429 on c-myc 3'UTR was confirmed. The levels of miR-429 in tumour tissue of patients with lymph node metastasis were significantly lower than in those without lymph node metastasis.
Conclusions:
Our results suggested that miR-429 played a role in the pathogenesis of gastric carcinoma and may function as a recessive cancer gene. c-myc is an important miR-429 target gene.
Insights
MicroRNA-429 (miR-429) is downregulated in gastric cancer, inhibiting cell viability and proliferation. It targets c-myc, suggesting miR-429 acts as a tumor suppressor in gastric carcinoma progression.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression.
- Dysregulation of miRNAs is implicated in various cancers, including gastric cancer.
- Investigating specific miRNAs like miR-429 is crucial for understanding cancer pathogenesis.
Purpose of the Study:
- To investigate the role and regulation of miR-429 in gastric cancer.
- To explore the underlying mechanisms of miR-429's influence on gastric cancer development.
- To identify downstream targets of miR-429 in gastric cancer cells.
Main Methods:
- Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for miR-429 expression analysis in patient tissues and cell lines.
- Bioinformatic analysis to predict potential downstream target genes of miR-429.
- Luciferase reporter assays and Western blot analysis to validate miR-429 targets and their functional impact on gene expression (e.g., c-myc).
Main Results:
- miR-429 expression was significantly downregulated in gastric cancer tissues and cells compared to normal tissues.
- Transfection with miR-429 mimics reduced cell viability, proliferation, and attachment in gastric cancer cells.
- miR-429 was confirmed to directly target the 3' untranslated region (3'UTR) of the c-myc gene, leading to decreased c-myc expression.
- Lower miR-429 levels correlated with lymph node metastasis in gastric cancer patients.
Conclusions:
- miR-429 functions as a tumor suppressor in gastric carcinoma, playing a role in its pathogenesis.
- c-myc is identified as a key downstream target gene of miR-429 in gastric cancer.
- The downregulation of miR-429 may contribute to gastric cancer progression and metastasis.
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