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Circular RNA circ-CHI3L1.2 modulates cisplatin resistance of osteosarcoma cells via the miR-340-5p/LPAATβ axis

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Abstract

Resistance to chemotherapy drugs is a major factor affecting the surgical outcome and prognosis of osteosarcoma patients. Circular RNAs (circRNAs) play an important role in tumor resistance to chemotherapy. In the present study, we aimed to investigate the role and mechanism of circRNA circ-chitinase 3-like 1.2 (CHI3L1.2) in resistance to cisplatin chemotherapy in osteosarcoma. We found that circ-CHI3L1.2 levels were higher in cisplatin-resistant cells than in their parent cells. circ-CHI3L1.2 knockdown decreased the half-maximal inhibitory concentration (IC50) of cisplatin and the expression levels of P-glycoprotein (P-gp), multidrug-resistance protein 1 (MRP1), and glutathione-S-transferase Pi1 (GSTP1), and promoted apoptosis of cisplatin-resistant osteosarcoma cells. In addition, circ-CHI3L1.2 knockdown induced mesenchymal to epithelial transition (MET) and suppressed cell migration and invasion. The competitive endogenous RNA (ceRNA) mechanism indicated that circ-CHI3L1.2 targets the micro-RNA (miR)-340-5p-lysophosphatidic acid acyltransferase β (LPAATβ) axis, and inhibition of miR-340-5p alleviates the effect of circ-CHI3L1.2 knockdown. In conclusion, circ-CHI3L1.2 levels were increased in cisplatin-resistant osteosarcoma cells and circ-CHI3L1.2 knockdown sensitized cisplatin-resistant osteosarcoma cells to cisplatin through the miR-340-5p-LPAATβ axis.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

circRNA:

Circular RNA

qRT-PCR:

Quantitative reverse transcription PCR

ceRNA:

Competitive endogenous RNA

siRNA:

Small interfering RNA

miR-NC:

Negative control miRNA

CCK8:

Cell counting Kit-8

IC50:

Inhibitory concentration 50

GSTs:

Glutathione S-transferases

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Funding

This study was supported by grants from the Clinical Science Foundation of Army Medical University (no. 2018XLC3018).

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Author notes

  1. Zehua Zhang and Qiang Zhou have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, First Affiliated Hospital, Army Medical University, No. 30 Gaotanyanzheng street, Chongqing, 400038, China

    Zehua Zhang, Fei Luo, Rui Zhou, Jianzhong Xu, Jun Xiao, Fei Dai & Lei Song

  2. Department of Orthopaedics, Third Affiliated Hospital, Medical University of Chongqing, Chongqing, 401120, China

    Qiang Zhou

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  1. Zehua Zhang
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Contributions

ZZ and QZ participated in the design of the study, most experiment, and writing the draft manuscript. FL and RZ carried out the statistical analysis. J-zX and JX were involved in the cell culture. FD and LS participated in the design of the study and the revision of draft manuscript. All the authors read and approved the final manuscript.

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Correspondence to Fei Dai or Lei Song.

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Zhang, Z., Zhou, Q., Luo, F. et al. Circular RNA circ-CHI3L1.2 modulates cisplatin resistance of osteosarcoma cells via the miR-340-5p/LPAATβ axis. Human Cell 34, 1558–1568 (2021). https://doi.org/10.1007/s13577-021-00564-6

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  • DOI: https://doi.org/10.1007/s13577-021-00564-6

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