Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5

Abstract

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.

Current progress and mechanisms of bone metastasis in lung cancer: a narrative review

“…Furthermore, DNA is of great significance. For example, by upregulating miR-660-5p and targeted SWItch/Sucrose Non-Fermentable (SWI/SNF) related, matrix associated, actin-dependent regulator of chromatin, subfamily A, member 5 (SMARCA5), Nm23-H1 causes inhibition of bone-specific metastasis (55).…”

Research progress on the molecular mechanisms of hepatic metastasis in lung cancer: a narrative review

“…Studies by Dash and others in 2010 showed that the downregulation of the SARI gene weakened IFN-β-induced tumor suppression (24). In 2009, the CD9, RHOA, and MYL12A genes, and in 2020, the Nm23-H1 gene, were found to be expressed in liver metastasis, and may be potential lung cancer suppressor genes in hepatic metastasis (25,32,35). It can cause the invasion and change of transfer.…”

“…2019 CUL5The accumulation of integrin β1 caused by the deletion of CUL5/SOCS3 can open up the downstream signaling pathway FAK/SRC and transfer SCLC.CUL5 and SOCS3, two components of the culling-ring E3 ubiquitin ligase complex, are candidate genes for inhibiting SCLC metastasis(28,34) 2020 Nm23-H1 Nm23-H1 gene is an inhibitor of tumor metastasis in lung cancer. By regulating the expression of specific metastasis-related genes and signaling pathway-related genes, the transfer of lung cancer cell L9981 can be changed to a certain extent(35) regulation in lung cancer is still unclear. Recent studies have found that miRNA-182 is significantly upregulated in a variety of solid tumors.…”

Personal Medicine and Bone Metastases: Biomarkers, Micro-RNAs and Bone Metastases

“…Micro-RNAs have been implicated in the mode of action of genes, which act to regulate lung cancer metastasis. The gene Nm23-H1 is a demonstrated inhibitor of lung cancer metastasis to bone, and qRT-PCR-based studies demonstrated that Nm23-H1 suppresses the expression of micro-RNA miR-660-5p [ 96 ]. Micro-RNA miR-660-5p has demonstrated ability to promote bone metastasis of lung cancer via regulation of the transcriptional regulator SMARCA5 [ 96 ].…”

“…The gene Nm23-H1 is a demonstrated inhibitor of lung cancer metastasis to bone, and qRT-PCR-based studies demonstrated that Nm23-H1 suppresses the expression of micro-RNA miR-660-5p [ 96 ]. Micro-RNA miR-660-5p has demonstrated ability to promote bone metastasis of lung cancer via regulation of the transcriptional regulator SMARCA5 [ 96 ]. Elucidation of the function of miR-660-5p reveals a network of transcriptional regulation via micro-RNAs and transcription factors operating within the bone metastasis of lung cancer.…”