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

Biology Direct

Lifeng Zheng¹  Yun Xie¹  Zonglin Chen²  Yiquan Zheng²  Yi Luo²  Jinhong Chen²  Shichun Wu²  Lulin Wang²  Wenxiang Lin² 

[1] Department of Orthopaedic Trauma, Trauma Center of Fujian, The First Affiliated Hospital of Fujian Medical University;Department of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical University;

关键词: LINC00426;    miR-4319;    Osteosarcoma;    Doxorubicin resistance;   

DOI  :  10.1186/s13062-020-00265-4

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown