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Circular RNA circRILPL1 promotes nasopharyngeal carcinoma malignant progression by activating the Hippo-YAP signaling pathway

Cell Death & Differentiation volume 30, pages 1679–1694 (2023)Cite this article

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Abstract

Circular RNAs (circRNAs) play an important regulatory role in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), which have not been thoroughly elucidated. In this study, we revealed for the first time that circRILPL1 was upregulated in NPC, weakened adhesion and decreased stiffness of NPC cells, and promoted NPC proliferation and metastasis in vitro and in vivo. Mechanistically, circRILPL1 inhibited the LATS1-YAP kinase cascade by binding to and activating ROCK1, resulting in decrease of YAP phosphorylation. Binding and cooperating with transport receptor IPO7, circRILPL1 promoted the translocation of YAP from the cytoplasm to the nucleus, where YAP enhanced the transcription of cytoskeleton remodeling genes CAPN2 and PXN. By which, circRILPL1 contributed to the pathogenesis of NPC. Our results demonstrated that circRILPL1 promoted the proliferation and metastasis of NPC through activating the Hippo-YAP signaling pathway by binding to both ROCK1 and IPO7. Highly expressed circRILPL1 in NPC may serve as an important biomarker for tumor diagnosis and may also be a potential therapeutic target.

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Fig. 1: CircRILPL1 is highly expressed in NPC and associated with poor prognosis of NPC patients.
Fig. 2: CircRILPL1 promotes NPC cells migration, invasion, proliferation and alters the mechanical properties of NPC cells in vitro.
Fig. 3: CircRILPL1 promotes the proliferation and metastasis of NPC cells in vivo.
Fig. 4: CircRILPL1 activates the Hippo-YAP signaling pathway.
Fig. 5: CircRILPL1 regulates NPC cells migration, invasion, proliferation and mechanical properties through YAP signaling.
Fig. 6: CircRILPL1 inhibits the LATS1-YAP kinase cascade by binding to ROCK1.
Fig. 7: CircRILPL1 promotes YAP nuclear translocation through mediating its binding to IPO7.
Fig. 8: CircRILPL1-YAP signaling promotes the transcription of CAPN2 and PXN.

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Data availability

All data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank Prof. Yong Li for providing pcDNA3.1(+) CircRNA Mini Vectors.

Funding

This study was funded by the National Natural Science Foundation of China (U21A20382, 82072374, 82002239, and 82272631), the Natural Science Foundation of Hunan Province (2023JJ30732 and 2021JJ41043).

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Authors and Affiliations

  1. NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410013, China

    Pan Wu, Xiangchan Hou, Miao Peng, Xiangying Deng, Chunmei Fan, Yongzhen Mo, Qianjin Liao, Hui Wang, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  2. Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, 410078, China

    Pan Wu, Xiangchan Hou, Miao Peng, Xiangying Deng, Chunmei Fan, Yongzhen Mo, Yumin Wang, Zheng Li, Fuyan Wang, Can Guo, Ming Zhou, Zhaoyang Zeng, Guiyuan Li, Wei Xiong & Bo Xiang

  3. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China

    Qijia Yan

  4. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China

    Yumin Wang & Weihong Jiang

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  1. Pan Wu
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Contributions

BX conceived and designed the project. PW completed the majority of experiments and wrote the manuscript. XH, MP, XD, QY, CF, YM, YW, ZL performed some of the experiments. FW, CG, MZ, ZZ and GL revised the manuscript. QL, HW and WJ collected tissue samples. WX and BX is responsible for research supervision and funding acquisition. All authors read and approved the final manuscript.

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Correspondence to Bo Xiang.

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Approval for the use of clinical samples and information was obtained from each patient and the Research Ethics Committee of Central South University. Written informed consent was received prior to patient participation. The animal experiments were conducted according to the protocol approved by the Animal Welfare Committee of Central South University.

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Wu, P., Hou, X., Peng, M. et al. Circular RNA circRILPL1 promotes nasopharyngeal carcinoma malignant progression by activating the Hippo-YAP signaling pathway. Cell Death Differ 30, 1679–1694 (2023). https://doi.org/10.1038/s41418-023-01171-8

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