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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-03-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.13308 |
| _version_ | 1818031402417913856 |
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| author | Cheng Ai Guangzhi Ma Yunfu Deng Qiangqiang Zheng Yingcai Gen Wen Li Yang Li Lingling Zu Qinghua Zhou |
| author_facet | Cheng Ai Guangzhi Ma Yunfu Deng Qiangqiang Zheng Yingcai Gen Wen Li Yang Li Lingling Zu Qinghua Zhou |
| author_sort | Cheng Ai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:50:54Z |
| format | Article |
| id | doaj.art-35def3297d2d4113a78d2bc8ac1985bd |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-12-10T05:50:54Z |
| publishDate | 2020-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-35def3297d2d4113a78d2bc8ac1985bd2022-12-22T02:00:03ZengWileyThoracic Cancer1759-77061759-77142020-03-0111364065010.1111/1759-7714.13308Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5Cheng Ai0Guangzhi Ma1Yunfu Deng2Qiangqiang Zheng3Yingcai Gen4Wen Li5Yang Li6Lingling Zu7Qinghua Zhou8Lung Cancer Center West China Hospital, Sichuan University Chengdu ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin ChinaTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin ChinaLung Cancer Center West China Hospital, Sichuan University Chengdu ChinaAbstract 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.https://doi.org/10.1111/1759-7714.13308Lung cancermiR‐660‐5pnm23‐H1RANKLSMARCA5 |
| spellingShingle | Cheng Ai Guangzhi Ma Yunfu Deng Qiangqiang Zheng Yingcai Gen Wen Li Yang Li Lingling Zu Qinghua Zhou Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 Thoracic Cancer Lung cancer miR‐660‐5p nm23‐H1 RANKL SMARCA5 |
| title | Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 |
| title_full | Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 |
| title_fullStr | Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 |
| title_full_unstemmed | Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 |
| title_short | Nm23‐H1 inhibits lung cancer bone‐specific metastasis by upregulating miR‐660‐5p targeted SMARCA5 |
| title_sort | nm23 h1 inhibits lung cancer bone specific metastasis by upregulating mir 660 5p targeted smarca5 |
| topic | Lung cancer miR‐660‐5p nm23‐H1 RANKL SMARCA5 |
| url | https://doi.org/10.1111/1759-7714.13308 |
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