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Ropivacaine suppresses the progression of renal cell carcinoma through regulating the lncRNA RMRP/EZH2/CCDC65 axis

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Abstract

Background

Renal cell carcinoma (RCC) is a common malignancy. Local anesthetics were displayed powerful effects against various cancers. This study aims to probe the functions and molecular mechanism of ropivacaine in RCC.

Methods

Different concentrations of ropivacaine were performed to administrate RCC cells including 786-O and Caki-1 cells. Cell viability and cell apoptosis were examined using CCK-8 and flow cytometry, respectively. Cell migration and invasion were determined by transwell assay. RMRP and CCDC65 expression was firstly predicted using TCGA dataset and further validated in RCC cells using qRT-PCR and western blot. The interactions among RMRP, EZH2 and CCDC65 were verified by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.

Results

Ropivacaine effectively suppressed RCC cell viability, migration and invasion and enhanced cell apoptosis rate. Aberrantly elevated RMRP expression in RCC tissues was predicted by TCGA database. Interestingly, overexpressed RMRP observed in RCC cells could be also blocked upon the administration of ropivacaine. Likewise, RMRP knockdown further strengthened ropivacaine-mediated tumor suppressive effects on RCC cells. In terms of mechanism, RMRP directly interacted with EZH2, thereby modulating the histone methylation of CCDC65 to silence its expression. Moreover, ropivacaine inhibited tumor growth in mice bearing RCC tumor through regulating RMRP/EZH2/CCDC65 axis.

Conclusion

In sum up, our work revealed that ropivacaine suppressed capacities of RCC cell viability, migration and invasion through modulating the RMRP/EZH2/CCDC65 axis, which laid the experimental foundation of ropivacaine for clinical application in the future.

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Data Availability

All data generated or analyzed during this study are included in this article. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Natural Science Foundation of Jiangxi Province(20192BAB205041).

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Authors and Affiliations

  1. Department of Anesthesiology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China

    Yingfen Xiong & Xiaolan Zheng

  2. Department of Medical Oncology, Jiangxi Cancer Hospital, No. 519, Jingdong Road, Qingshanhu District, Nanchang, 330029, Jiangxi Province, People’s Republic of China

    Huangying Deng

Authors
  1. Yingfen Xiong
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  2. Xiaolan Zheng
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  3. Huangying Deng
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Contributions

Yingfen Xiong: acquisition of data; analysis and interpretation of data; drafting the manuscript.

Xiaolan Zheng: acquisition of data; drafting the manuscript.

Huangying Deng: conception and design of study; revising the manuscript critically for important intellectual content.

Corresponding author

Correspondence to Huangying Deng.

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These authors declared no competing interests in this work.

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Highlights

1. Ropivacaine evidently inhibited the capacities of RCC cell viability, migration and invasion.

2. Ropivacaine exhibited anti-tumor biological effects on RCC cells via downregulating RMRP expression.

3. RMRP epigenetically repressed CCDC65 expression via recruiting EZH2.

4. Ropivacaine inhibited tumor growth of mice bearing RCC tumor through regulating the RMRP/EZH2/CCDC65 axis.

Supplementary Information

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Supplementary file1 (DOCX 13 KB)

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Xiong, Y., Zheng, X. & Deng, H. Ropivacaine suppresses the progression of renal cell carcinoma through regulating the lncRNA RMRP/EZH2/CCDC65 axis. DARU J Pharm Sci 32, 121–132 (2024). https://doi.org/10.1007/s40199-023-00492-w

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