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microRNA-107 inhibits gastric cancer cell proliferation and metastasis by targeting PI3K/AKT pathway
Feng Cheng1, Zhijun Yang2, Fei Huang1
1Clinical Laboratory, Ezhou Central Hospital, Ezhou, Hubei, 436000, China.
Abstract:
The present study was aimed to investigate the effect of miR-107 transfection on gastric cancer cell growth. Results from qRT-PCR revealed that level of miR-107 in SGC-7901 and MKN1 cell lines was down-regulated in comparison to the normal cells, GES-1. CCK-8 assay revealed a significant reduction in the proliferation of SGC-7901 cells on transfection with miR-107. The tumor growth was very slow in the mice implanted with SGC-7901/miR-107 compared to those bearing SGC-7901/miR-NC. In SGC-7901 cells metastasis potential after miR-107 transfection was examined using wound-healing and Transwell invasion assays. The migration as well as invasion potential of SGC-7901 cells was significantly lower on transfection with miR-107. The activity of luciferase was reduced markedly in SGC-7901 cells co-transfected with miR-107 mimic compared to miR-NC. However, miR-107 mimic co-transfection did not affect the luciferase activity in SGC-7901 cells bearing mutant-type BDNF 3'UTR. Western blot assay showed that miR-107 overexpression causes inhibition of BDNF mRNA and protein expression in SGC-7901 cells. The CCK8 assay showed that pBDNF transfection prevented miR-107 mediated inhibition of SGC-7901 cell proliferation. miR-107 mimic transfection inhibited expression of BDNF and activation of PI3K (p-PI3K) and AKT (p-AKT) in SGC-7901 cells. In order to confirm whether activation of PI3K and AKT by miR-107 mimic involves inhibition of BDNF, the cells were co-transfected with si-BDNF. The results revealed that si-BDNF transfection led to inhibition of BDNF expression and PI3K and AKT activation in SGC-7901 cells. In summary, the present study demonstrates that miR-107 expression inhibits proliferation and metastasis in gastric cancer cells. Therefore, miR-107 acts as tumor inhibitor for gastric cancer through targeting BDNF expression. Thus miR-107 can be used for treatment of gastric cancer.
Insights
MicroRNA-107 (miR-107) acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation and metastasis. This study shows miR-107 targets BDNF, offering a potential therapeutic strategy for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer is a leading cause of cancer-related deaths worldwide.
- Dysregulation of microRNAs (miRNAs) is implicated in gastric cancer development and progression.
- miR-107 has been identified as a potential tumor suppressor, but its precise role in gastric cancer requires further investigation.
Purpose of the Study:
- To investigate the effect of miR-107 on gastric cancer cell proliferation and metastasis.
- To elucidate the molecular mechanism underlying miR-107's function in gastric cancer.
- To evaluate the therapeutic potential of miR-107 in gastric cancer treatment.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to assess miR-107 levels.
- Cell Counting Kit-8 (CCK-8) assay for cell proliferation.
- In vivo tumor growth assays in mice.
- Wound-healing and Transwell assays for cell migration and invasion.
- Luciferase reporter assays to validate target genes.
- Western blot analysis for protein expression.
- Transfection with miR-107 mimics, negative controls, and si-BDNF.
Main Results:
- miR-107 expression was significantly downregulated in gastric cancer cell lines (SGC-7901, MKN1) compared to normal cells (GES-1).
- miR-107 transfection inhibited proliferation, tumor growth, migration, and invasion of SGC-7901 cells.
- miR-107 directly targeted BDNF (Brain-Derived Neurotrophic Factor), reducing its mRNA and protein expression.
- miR-107 overexpression inhibited the PI3K/AKT signaling pathway.
- Restoring BDNF expression or inhibiting BDNF expression reversed the effects of miR-107 on proliferation and signaling pathways.
Conclusions:
- miR-107 functions as a tumor suppressor in gastric cancer by inhibiting cell proliferation and metastasis.
- miR-107 exerts its tumor-suppressive effects by targeting BDNF and subsequently inhibiting the PI3K/AKT pathway.
- miR-107 holds promise as a potential therapeutic agent for gastric cancer.
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