MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma
Hua-chun Rao,1,* Zhao-ke Wu,1,* Si-da Wei,1 Yun Jiang,1 Qing-xin Guo,1 Jia-wen Wang,1 Chang-xian Chen,1 Hui-yong Yang2 1Quanzhou Orthopedic-Traumatological Hospital, Fengze District, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Institute of Molecular Medicine, Huaqiao...
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doaj-f7637474b7b04cdfb709dc3b9d25d2cd2020-11-25T03:13:18ZengDove Medical PressCancer Management and Research1179-13222020-09-01Volume 128989900157321MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in OsteosarcomaRao HWu ZWei SJiang YGuo QWang JChen CYang HHua-chun Rao,1,* Zhao-ke Wu,1,* Si-da Wei,1 Yun Jiang,1 Qing-xin Guo,1 Jia-wen Wang,1 Chang-xian Chen,1 Hui-yong Yang2 1Quanzhou Orthopedic-Traumatological Hospital, Fengze District, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Institute of Molecular Medicine, Huaqiao University, Quanzhou, People’s Republic of China*These authors contributed equally to this work.Correspondence: Chang-xian Chen Tel +86 13636913112Email ccx6070@qq.comHui-yong Yang Tel +86 15359531722Email shyhy@hqu.edu.cnPurpose: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma.Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments.Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61.Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.Keywords: Merlin, miR-25-3p, osteosarcoma, proliferation, apoptosis, metastasishttps://www.dovepress.com/mir-25-3p-serves-as-an-oncogenic-microrna-by-downregulating-the-expres-peer-reviewed-article-CMARmerlinmir-25-3posteosarcomaproliferationapoptosismetastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rao H Wu Z Wei S Jiang Y Guo Q Wang J Chen C Yang H |
spellingShingle |
Rao H Wu Z Wei S Jiang Y Guo Q Wang J Chen C Yang H MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma Cancer Management and Research merlin mir-25-3p osteosarcoma proliferation apoptosis metastasis |
author_facet |
Rao H Wu Z Wei S Jiang Y Guo Q Wang J Chen C Yang H |
author_sort |
Rao H |
title |
MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma |
title_short |
MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma |
title_full |
MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma |
title_fullStr |
MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma |
title_full_unstemmed |
MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma |
title_sort |
mir-25-3p serves as an oncogenic microrna by downregulating the expression of merlin in osteosarcoma |
publisher |
Dove Medical Press |
series |
Cancer Management and Research |
issn |
1179-1322 |
publishDate |
2020-09-01 |
description |
Hua-chun Rao,1,* Zhao-ke Wu,1,* Si-da Wei,1 Yun Jiang,1 Qing-xin Guo,1 Jia-wen Wang,1 Chang-xian Chen,1 Hui-yong Yang2 1Quanzhou Orthopedic-Traumatological Hospital, Fengze District, Quanzhou, Fujian, People’s Republic of China; 2School of Medicine, Institute of Molecular Medicine, Huaqiao University, Quanzhou, People’s Republic of China*These authors contributed equally to this work.Correspondence: Chang-xian Chen Tel +86 13636913112Email ccx6070@qq.comHui-yong Yang Tel +86 15359531722Email shyhy@hqu.edu.cnPurpose: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma.Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments.Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61.Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.Keywords: Merlin, miR-25-3p, osteosarcoma, proliferation, apoptosis, metastasis |
topic |
merlin mir-25-3p osteosarcoma proliferation apoptosis metastasis |
url |
https://www.dovepress.com/mir-25-3p-serves-as-an-oncogenic-microrna-by-downregulating-the-expres-peer-reviewed-article-CMAR |
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