Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma

Abstract Background LINC00426 is a newly identified long non-coding RNA (lncRNA) with unacknowledged biological roles. Here we set out to characterize the expression status of LINC00426 in osteosarcoma and understand its mechanistic involvement in incidence of doxorubicin (Dox) resistance. Methods T...

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Main Authors: Lulin Wang, Yi Luo, Yiquan Zheng, Lifeng Zheng, Wenxiang Lin, Zonglin Chen, Shichun Wu, Jinhong Chen, Yun Xie
Format: Article
Language:English
Published: BMC 2020-07-01
Series:Biology Direct
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13062-020-00265-4
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author Lulin Wang
Yi Luo
Yiquan Zheng
Lifeng Zheng
Wenxiang Lin
Zonglin Chen
Shichun Wu
Jinhong Chen
Yun Xie
author_facet Lulin Wang
Yi Luo
Yiquan Zheng
Lifeng Zheng
Wenxiang Lin
Zonglin Chen
Shichun Wu
Jinhong Chen
Yun Xie
author_sort Lulin Wang
collection DOAJ
description Abstract Background LINC00426 is a newly identified long non-coding RNA (lncRNA) with unacknowledged biological roles. Here we set out to characterize the expression status of LINC00426 in osteosarcoma and understand its mechanistic involvement in incidence of doxorubicin (Dox) resistance. Methods The relative expression of LINC00426 and miR-4319 was determined by real-time PCR. Cell viability and proliferation in response to LINC00426 silencing or miR-4319 over-expression was measured with CCK-8 kit and colony formation assay, respectively. The direct association between LINC00426 and miR-4319 was analyzed by pulldown assay with biotin-labelled probes. Results LINC00426 was significantly up-regulated in Dox-resistant osteosarcoma (OS) both in vitro and in vivo, which intimately associated with unfavorable prognosis. SiRNA-mediated knockdown of LINC00426 remarkably compromised cell viability and proliferation in Dox-resistant OS cells, which accompanied with decrease of IC50 and activation of caspase-3. We further predicted and validated the regulatory effects of miR-4319 on LINC00426 expression. Simultaneously, we provided evidences in support of direct binding between LINC00426 and miR-4319 by pulldown assay. Reciprocally negative regulation was observed between LINC00426 and miR-4319 each other. Conclusion Ectopic introduction of miR-4319 significantly surmounted the Dox resistance in OS cells, while miR-4319 inhibition in LINC00426-deficient cells greatly restore this phenotype. We uncovered the important contribution of LINC00426/miR-4319 to Dox resistance in osteosarcoma. Reviewers This article was reviewed by Bo Liang and Sinan Zhu.
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spelling doaj.art-d0cbf3287f7c45deb4f2546ee7158fdf2022-12-21T23:09:07ZengBMCBiology Direct1745-61502020-07-0115111110.1186/s13062-020-00265-4Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcomaLulin Wang0Yi Luo1Yiquan Zheng2Lifeng Zheng3Wenxiang Lin4Zonglin Chen5Shichun Wu6Jinhong Chen7Yun Xie8Department of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedic Trauma, Trauma Center of Fujian, The First Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical UniversityDepartment of Orthopaedic Trauma, Trauma Center of Fujian, The First Affiliated Hospital of Fujian Medical UniversityAbstract Background LINC00426 is a newly identified long non-coding RNA (lncRNA) with unacknowledged biological roles. Here we set out to characterize the expression status of LINC00426 in osteosarcoma and understand its mechanistic involvement in incidence of doxorubicin (Dox) resistance. Methods The relative expression of LINC00426 and miR-4319 was determined by real-time PCR. Cell viability and proliferation in response to LINC00426 silencing or miR-4319 over-expression was measured with CCK-8 kit and colony formation assay, respectively. The direct association between LINC00426 and miR-4319 was analyzed by pulldown assay with biotin-labelled probes. Results LINC00426 was significantly up-regulated in Dox-resistant osteosarcoma (OS) both in vitro and in vivo, which intimately associated with unfavorable prognosis. SiRNA-mediated knockdown of LINC00426 remarkably compromised cell viability and proliferation in Dox-resistant OS cells, which accompanied with decrease of IC50 and activation of caspase-3. We further predicted and validated the regulatory effects of miR-4319 on LINC00426 expression. Simultaneously, we provided evidences in support of direct binding between LINC00426 and miR-4319 by pulldown assay. Reciprocally negative regulation was observed between LINC00426 and miR-4319 each other. Conclusion Ectopic introduction of miR-4319 significantly surmounted the Dox resistance in OS cells, while miR-4319 inhibition in LINC00426-deficient cells greatly restore this phenotype. We uncovered the important contribution of LINC00426/miR-4319 to Dox resistance in osteosarcoma. Reviewers This article was reviewed by Bo Liang and Sinan Zhu.http://link.springer.com/article/10.1186/s13062-020-00265-4LINC00426miR-4319OsteosarcomaDoxorubicin resistance
spellingShingle Lulin Wang
Yi Luo
Yiquan Zheng
Lifeng Zheng
Wenxiang Lin
Zonglin Chen
Shichun Wu
Jinhong Chen
Yun Xie
Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
Biology Direct
LINC00426
miR-4319
Osteosarcoma
Doxorubicin resistance
title Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
title_full Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
title_fullStr Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
title_full_unstemmed Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
title_short Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
title_sort long non coding rna linc00426 contributes to doxorubicin resistance by sponging mir 4319 in osteosarcoma
topic LINC00426
miR-4319
Osteosarcoma
Doxorubicin resistance
url http://link.springer.com/article/10.1186/s13062-020-00265-4
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