Nm23-H1 inhibits lung cancer bone-specific metastasis by upregulating miR-660-5p targeted SMARCA5.
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.
['Ai|Cheng|C|', 'Ma|Guangzhi|G|', 'Deng|Yunfu|Y|', 'Zheng|Qiangqiang|Q|', 'Gen|Yingcai|Y|', 'Li|Wen|W|', 'Li|Yang|Y|', 'Zu|Lingling|L|', 'Zhou|Qinghua|Q|0000-0002-1108-9456']
D000251:Adenosine Triphosphatases D000818:Animals D017209:Apoptosis D014408:Biomarkers, Tumor D001859:Bone Neoplasms D049109:Cell Proliferation D002868:Chromosomal Proteins, Non-Histone D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008175:Lung Neoplasms D051379:Mice D008819:Mice, Nude D035683:MicroRNAs D054778:NM23 Nucleoside Diphosphate Kinases D009361:Neoplasm Invasiveness D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
nm23-H1 Lung cancer miR-660-5p SMARCA5 RANKL