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Long non-coding RNA LINC00426 contributes to doxorubicin resistance by sponging miR-4319 in osteosarcoma
Lulin Wang1, Yi Luo1, Yiquan Zheng1
1Department of Orthopaedics, Zhangzhou Affiliated Hospital of Fujian Medical University, No.59, Shengli Road West, Xiang Cheng District, Zhangzhou, 363000, Fujian, China.
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.
Insights
The long non-coding RNA LINC00426 is upregulated in doxorubicin-resistant osteosarcoma, contributing to drug resistance. Targeting LINC00426 or enhancing miR-4319 can overcome this resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone malignancy.
- Doxorubicin (Dox) is a common chemotherapeutic agent for OS.
- Doxorubicin resistance is a major challenge in OS treatment.
Purpose of the Study:
- To investigate the expression of LINC00426 in osteosarcoma.
- To elucidate the role of LINC00426 in doxorubicin resistance in OS.
- To explore the regulatory relationship between LINC00426 and miR-4319.
Main Methods:
- Real-time PCR to quantify LINC00426 and miR-4319 expression.
- Cell Counting Kit-8 (CCK-8) and colony formation assays for cell viability and proliferation.
- Pulldown assays to confirm direct binding between LINC00426 and miR-4319.
Main Results:
- LINC00426 was significantly upregulated in Dox-resistant OS cells and tissues.
- Knockdown of LINC00426 reduced cell viability, proliferation, and chemosensitivity in Dox-resistant OS cells.
- LINC00426 directly binds to and reciprocally regulates miR-4319.
Conclusions:
- LINC00426 plays a crucial role in mediating doxorubicin resistance in osteosarcoma.
- The LINC00426/miR-4319 axis is a potential therapeutic target for overcoming Dox resistance in OS.
- Restoring miR-4319 levels can effectively combat Dox resistance in osteosarcoma.
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