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Published on: March 30, 2019
Nm23-H1 inhibits lung cancer bone-specific metastasis by upregulating miR-660-5p targeted SMARCA5
Cheng Ai1,2, Guangzhi Ma1, Yunfu Deng1
1Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Background:
Nm23-H1 gene has been found to be an inhibitor of tumor metastasis in lung cancer. MicroRNAs (miRNAs) play key roles in tumor metastasis through multiple signaling pathways. This study explored whether the nm23-H1 gene could inhibit invasion and metastasis of lung cancer cells by regulating miRNA-660-5p targets.
Methods:
Quantitative real-time PCR (qRT-PCR) and western blots were used to measure the expression of nm23-H1 and miR-660-5p of various human lung cancer cell lines. Cell counting kit-8 (CCK-8), wound-healing and transwell assay were carried out to assess cell proliferation, migration and invasion of each cell line. Xenograft were applied to determine in vivo effects of miR-660-5p among nude mice. Luciferase assay and western blot were performed to determine the target gene of miR-660-5p.
Results:
We found that high expression of nm23-H1 correlated with decreased miRNA-660-5p expression. Inhibiting miR-660-5p suppressed lung cancer cells progression significantly in vitro, whereas overexpression of miR-660-5p facilitated tumor growth and bone metastasis in vivo. In addition, as the potential target gene of miR-660-5p, SMARCA5 overexpression in vitro suppressed tumor progression and osteolytic metastasis associated RANKL signaling, which is congruent with the effect of nm23-H1 on the lung cancer cells.
Conclusion:
Nm23-H1 inhibits tumor progression and bone-specific metastasis of lung cancer by regulating miR-660-5p/SMARCA5/RANKL axis, which indicates the related genes may serve as potential targets for the treatment of human lung cancer.
Key Points:
Significant findings of the study High expression of nm23-H1 correlated with decreased miRNA-660-5p expression. Further, downregulation of miR-660-5p significantly suppressed the tumor progression and bone-specific metastasis of lung cancer cells. What this study adds This is the first study to show an inverse association between nm23-H1 and miR-660-5p, and confirm that nm23-H1 inhibits tumor progression and bone-specific metastasis of lung cancer by regulating miR-660-5p/SMARCA5/RANKL axis.
Insights
Nm23-H1 inhibits lung cancer metastasis by regulating microRNA-660-5p (miR-660-5p). This study found that high nm23-H1 expression correlates with low miR-660-5p, and this pathway is crucial for controlling tumor progression and bone metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The nm23-H1 gene is recognized as a suppressor of tumor metastasis in lung cancer.
- MicroRNAs (miRNAs) significantly influence tumor metastasis through various signaling pathways.
Purpose of the Study:
- To investigate if the nm23-H1 gene inhibits lung cancer cell invasion and metastasis.
- To determine the role of nm23-H1 in regulating miRNA-660-5p (miR-660-5p) targets.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and western blots were used to analyze nm23-H1 and miR-660-5p expression.
- Cell proliferation, migration, and invasion were assessed using CCK-8, wound-healing, and transwell assays.
- In vivo effects were studied in nude mice xenografts, with target gene identification via luciferase and western blot assays.
Main Results:
- High nm23-H1 expression was inversely correlated with miR-660-5p levels.
- Inhibition of miR-660-5p suppressed lung cancer progression in vitro.
- Overexpression of miR-660-5p promoted tumor growth and bone metastasis in vivo, with SMARCA5 identified as a target gene.
Conclusions:
- Nm23-H1 inhibits lung cancer progression and bone metastasis by regulating the miR-660-5p/SMARCA5/RANKL axis.
- These findings suggest that the nm23-H1/miR-660-5p/SMARCA5/RANKL pathway represents a potential therapeutic target for lung cancer treatment.
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