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Long non-coding RNA long intergenic non-coding 00641 mediates cell progression with stimulating cisplatin-resistance
JinShan Tang1,2, ZiQiang Zhu3,4, Suwei Dong3,4
1Department of Orthopedic, The Second People's Hospital of Huai'an, Huai'an City, Jiangsu Province, China.
Abstract:
As a staple chemotherapy medicine, cisplatin (DDP) is extensively applied in cancer patients, but its drug resistance is limited. Numerous studies have elucidated that long non-coding RNA (lncRNA) performs as a pivotal agent in osteosarcoma (OS). Nevertheless, lncRNA long intergenic non-coding 00641 (LINC00641)'s functions in DDP resistance for OS remain obscure. The purpose of this study was to investigate the effect and mechanism of LINC00641 on drug resistance of OS. The tissues of both clinical cancer patients and the normal control were gathered. Detection of LINC00641, microRNA-320d (miR-320d) and myeloid cell leukemia-1 (MCL1) was conducted. After the selection of OS cell lines, the detection of cell advancement was applied. Series of experiments were conducted to verify the interaction of LINC00641, miR-320d and MCL1. Xenografted tumor model in vivo was utilized to determine the function of LINC00641. The data displayed, LINC00641 was prominently elevated in OS tissues and cells, especially in DDP-resistant tumors and cell lines. Knock-down LINC00641 was able to attenuate progression of DDP-resistant OS cells thus dampening their drug resistance toward DDP. Moreover, knock-downing LINC00641 gene was also able to manifest antagonism toward DDP-resistance in vivo. On the grounds of bioinformatics prediction, a direct binding of LINC00641 with miR-320d existed, whose target was MCL1. Meanwhile, LINC00641 modulated MCL1 via targeting miR-320d. Additionally, repressive LINC00641 blocked MCL1 via emulative interaction with miR-320d, thus expediting DDP-sensitivity of OS cells. All in all, it is found that LINC00641 is available to escalate drug resistance of DDP-resistant OS cells via mediation of miR-320d/MCL1 axis.
Insights
Long non-coding RNA LINC00641 promotes cisplatin resistance in osteosarcoma by regulating the miR-320d/MCL1 pathway. Reducing LINC00641 enhances chemotherapy sensitivity in osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cisplatin (DDP) is a key chemotherapy drug for osteosarcoma (OS), but drug resistance limits its efficacy.
- Long non-coding RNAs (lncRNAs) are implicated in OS development, yet the role of LINC00641 in DDP resistance is unclear.
Purpose of the Study:
- To investigate the function and mechanism of lncRNA LINC00641 in DDP resistance in osteosarcoma.
Main Methods:
- Analysis of LINC00641, miR-320d, and MCL1 expression in clinical OS tissues and cell lines.
- In vitro experiments assessing cell progression and drug resistance after LINC00641 manipulation.
- Verification of molecular interactions using bioinformatics and experimental assays.
- In vivo xenograft models to evaluate LINC00641's role in DDP resistance.
Main Results:
- LINC00641 expression was significantly upregulated in OS tissues and cells, particularly in DDP-resistant samples.
- Knockdown of LINC00641 reduced OS cell progression and DDP resistance in vitro and in vivo.
- LINC00641 directly binds to miR-320d, modulating MCL1 expression and promoting DDP resistance via the miR-320d/MCL1 axis.
Conclusions:
- LINC00641 acts as a crucial oncogenic lncRNA that enhances DDP resistance in osteosarcoma.
- Targeting the LINC00641/miR-320d/MCL1 pathway may represent a therapeutic strategy to overcome DDP resistance in OS.
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