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CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

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Abstract

Aberrant expression of circular RNAs (circRNAs) is frequently linked to colorectal cancer (CRC). Here, we identified circZFR as a promising biomarker for CRC diagnosis and prognosis. CircZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence, advanced-stages, and metastasis. In both in vitro and in vivo settings, circZFR promoted the growth and spread while suppressing apoptosis of CRC. Exosomes with circZFR overexpression promoted the proliferation and migration of cocultured CRC cells. Mechanistically, epithelial splicing regulatory protein 1 (ESRP1) in CRC cells may enhance the production of circZFR. BCL2-associated transcription factor 1 (BCLAF1) bound to circZFR, which prevented its ubiquitinated degradation. Additionally, circZFR sponged miR-3127-5p to boost rhotekin 2 (RTKN2) expression. Our TCP1-CD-QDs nanocarrier was able to carry and deliver circZFR siRNA (si-circZFR) to the vasculature of CRC tissues and cells, which inhibited the growth of tumors in patient-derived xenograft (PDX) models. Taken together, our results show that circZFR is an oncogenic circRNA, which promotes the development and spread of CRC in a BCLAF1 and miR-3127-5p-dependent manner. CircZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.

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References

  • Abdelmohsen, K., Panda, A.C., Munk, R., Grammatikakis, I., Dudekula, D.B., De, S., Kim, J., Noh, J.H., Kim, K.M., Martindale, J.L., et al. (2017). Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol 14, 361–369.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ashwal-Fluss, R., Meyer, M., Pamudurti, N.R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., and Kadener, S. (2014). circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56, 55–66.

    Article  CAS  PubMed  Google Scholar 

  • Bertrand, N., Wu, J., Xu, X., Kamaly, N., and Farokhzad, O.C. (2014). Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66, 2–25.

    Article  CAS  PubMed  Google Scholar 

  • Chen, D., Love, K.T., Chen, Y., Eltoukhy, A.A., Kastrup, C., Sahay, G., Jeon, A., Dong, Y., Whitehead, K.A., and Anderson, D.G. (2012). Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J Am Chem Soc 134, 6948–6951.

    Article  CAS  PubMed  Google Scholar 

  • Chen, J., Wu, Y., Luo, X., Jin, D., Zhou, W., Ju, Z., Wang, D., Meng, Q., Wang, H., Fu, X., et al. (2021). Circular RNA circRHOBTB3 represses metastasis by regulating the HuR-mediated mRNA stability of PTBP1 in colorectal cancer. Theranostics 11, 7507–7526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, J., Wu, Y., Zhang, L., Fang, X., and Hu, X. (2019a). Evidence for calpains in cancer metastasis. J Cell Physiol 234, 8233–8240.

    Article  CAS  PubMed  Google Scholar 

  • Chen, L.L. (2020). The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol 21, 475–490.

    Article  CAS  PubMed  Google Scholar 

  • Chen, N., Zhao, G., Yan, X., Lv, Z., Yin, H., Zhang, S., Song, W., Li, X., Li, L., Du, Z., et al. (2018). A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulating TET1 and DNMT1. Genome Biol 19, 218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, Q., Mang, G., Wu, J., Sun, P., Li, T., Zhang, H., Wang, N., Tong, Z., Wang, W., Zheng, Y., et al. (2020). Circular RNA circSnx5 controls immunogenicity of dendritic cells through the miR-544/SOCS1 axis and PU.1 activity regulation. Mol Ther 28, 2503–2518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, R.X., Chen, X., Xia, L.P., Zhang, J.X., Pan, Z.Z., Ma, X.D., Han, K., Chen, J.W., Judde, J.G., Deas, O., et al. (2019b). N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. Nat Commun 10, 4695.

    Article  PubMed  PubMed Central  Google Scholar 

  • Conn, S.J., Pillman, K.A., Toubia, J., Conn, V.M., Salmanidis, M., Phillips, C.A., Roslan, S., Schreiber, A.W., Gregory, P.A., and Goodall, G.J. (2015). The RNA binding protein quaking regulates formation of circRNAs. Cell 160, 1125–1134.

    Article  CAS  PubMed  Google Scholar 

  • Dekker, E., Tanis, P.J., Vleugels, J.L.A., Kasi, P.M., and Wallace, M.B. (2019). Colorectal cancer. Lancet 394, 1467–1480.

    Article  PubMed  Google Scholar 

  • Du, W.W., Fang, L., Yang, W., Wu, N., Awan, F.M., Yang, Z., and Yang, B.B. (2017). Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ 24, 357–370.

    Article  CAS  PubMed  Google Scholar 

  • Du, W.W., Yang, W., Liu, E., Yang, Z., Dhaliwal, P., and Yang, B.B. (2016). Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44, 2846–2858.

    Article  PubMed  PubMed Central  Google Scholar 

  • El-Andaloussi, S., Lee, Y., Lakhal-Littleton, S., Li, J., Seow, Y., Gardiner, C., Alvarez-Erviti, L., Sargent, I.L., and Wood, M.J.A. (2012). Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc 7, 2112–2126.

    Article  CAS  PubMed  Google Scholar 

  • Ferguson, S.W., and Nguyen, J. (2016). Exosomes as therapeutics: the implications of molecular composition and exosomal heterogeneity. J Control Release 228, 179–190.

    Article  CAS  PubMed  Google Scholar 

  • Garbayo, E., Pascual-Gil, S., Rodríguez-Nogales, C., Saludas, L., Estella-Hermoso de Mendoza, A., and Blanco-Prieto, M.J. (2020). Nanomedicine and drug delivery systems in cancer and regenerative medicine. WIREs Nanomed Nanobiotechnol 12, e1637.

    Article  CAS  Google Scholar 

  • Hansen, T.B., Jensen, T.I., Clausen, B.H., Bramsen, J.B., Finsen, B., Damgaard, C.K., and Kjems, J. (2013). Natural RNA circles function as efficient microRNA sponges. Nature 495, 384–388.

    Article  CAS  PubMed  Google Scholar 

  • He, A.T., Liu, J., Li, F., and Yang, B.B. (2021). Targeting circular RNAs as a therapeutic approach: current strategies and challenges. Sig Transduct Target Ther 6, 185.

    Article  CAS  Google Scholar 

  • Holdt, L.M., Stahringer, A., Sass, K., Pichler, G., Kulak, N.A., Wilfert, W., Kohlmaier, A., Herbst, A., Northoff, B.H., Nicolaou, A., et al. (2016). Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun 7, 12429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu, W., Liu, C., Bi, Z.Y., Zhou, Q., Zhang, H., Li, L.L., Zhang, J., Zhu, W., Song, Y.Y.Y., Zhang, F., et al. (2020). Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology. Mol Cancer 19, 102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jarlstad Olesen, M.T., and Kristensen, L.S. (2021). Circular RNAs as microRNA sponges: evidence and controversies. Essays Biochem 65, 685–696.

    Article  PubMed  Google Scholar 

  • Kamerkar, S., Lebleu, V.S., Sugimoto, H., Yang, S., Ruivo, C.F., Melo, S.A., Lee, J.J., and Kalluri, R. (2017). Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanth, P., and Inadomi, J.M. (2021). Screening and prevention of colorectal cancer. BMJ 374, n1855.

    Article  PubMed  Google Scholar 

  • Komander, D. (2009). The emerging complexity of protein ubiquitination. Biochem Soc Trans 37, 937–953.

    Article  CAS  PubMed  Google Scholar 

  • Kristensen, L.S., Andersen, M.S., Stagsted, L.V.W., Ebbesen, K.K., Hansen, T.B., and Kjems, J. (2019). The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20, 675–691.

    Article  CAS  PubMed  Google Scholar 

  • Kristensen, L.S., Ebbesen, K.K., Sokol, M., Jakobsen, T., Korsgaard, U., Eriksen, A.C., Hansen, T.B., Kjems, J., and Hager, H. (2020). Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory. Nat Commun 11, 4551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kristensen, L.S., Jakobsen, T., Hager, H., and Kjems, J. (2022). The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol 19, 188–206.

    Article  CAS  PubMed  Google Scholar 

  • Li, H., Ma, X., and Li, H. (2019). Intriguing circles: conflicts and controversies in circular RNA research. WIREs RNA 10, e1538.

    Article  PubMed  Google Scholar 

  • Li, J., Gao, X., Zhang, Z., Lai, Y., Lin, X., Lin, B., Ma, M., Liang, X., Li, X., Lv, W., et al. (2021). CircCD44 plays oncogenic roles in triple-negative breast cancer by modulating the miR-502-5p/KRAS and IGF2BP2/Myc axes. Mol Cancer 20, 138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., Chen, D., Gu, J., He, X., and Huang, S. (2015). Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25, 981–984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang, G., Yang, Y., Niu, G., Tang, Z., and Li, K. (2017). Genome-wide profiling of Sus scrofa circular RNAs across nine organs and three developmental stages. DNA Res 24, 523–535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorenzi, L., Chiu, H.S., Avila Cobos, F., Gross, S., Volders, P.J., Cannoodt, R., Nuytens, J., Vanderheyden, K., Anckaert, J., Lefever, S., et al. (2021). The RNA Atlas expands the catalog of human non-coding RNAs. Nat Biotechnol 39, 1453–1465.

    Article  CAS  PubMed  Google Scholar 

  • Ma, X., Zhao, Y., and Liang, X.J. (2011). Theranostic nanoparticles engineered for clinic and pharmaceutics. Acc Chem Res 44, 1114–1122.

    Article  CAS  PubMed  Google Scholar 

  • Merlino, G., Miodini, P., Callari, M., D’Aiuto, F., Cappelletti, V., and Daidone, M.G. (2017). Prognostic and functional role of subtype-specific tumor-stroma interaction in breast cancer. Mol Oncol 11, 1399–1412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore, L., Yang, J., Lan, T.T.H., Osawa, E., Lee, D.K., Johnson, W.D., Xi, J., Chow, E.K.H., and Ho, D. (2016). Biocompatibility assessment of detonation nanodiamond in non-human primates and rats using histological, hematologic, and urine analysis. ACS Nano 10, 7385–7400.

    Article  CAS  PubMed  Google Scholar 

  • Okholm, T.L.H., Sathe, S., Park, S.S., Kamstrup, A.B., Rasmussen, A.M., Shankar, A., Chua, Z.M., Fristrup, N., Nielsen, M.M., Vang, S., et al. (2020). Transcriptome-wide profiles of circular RNA and RNA-binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression. Genome Med 12, 112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pang, X., Li, R., Shi, D., Pan, X., Ma, C., Zhang, G., Mu, C., and Chen, W. (2017). Knockdown of Rhotekin 2 expression suppresses proliferation and induces apoptosis in colon cancer cells. Oncol Lett 14, 8028–8034.

    PubMed  PubMed Central  Google Scholar 

  • Qiu, S., Li, B., Xia, Y., Xuan, Z., Li, Z., Xie, L., Gu, C., Lv, J., Lu, C., Jiang, T., et al. (2022). CircTHBS1 drives gastric cancer progression by increasing INHBA mRNA expression and stability in a ceRNA- and RBP-dependent manner. Cell Death Dis 13, 266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruan, H., Xiang, Y., Ko, J., Li, S., Jing, Y., Zhu, X., Ye, Y., Zhang, Z., Mills, T., Feng, J., et al. (2019). Comprehensive characterization of circular RNAs in ∼ 1000 human cancer cell lines. Genome Med 11, 55.

    Article  PubMed  PubMed Central  Google Scholar 

  • Santer, L., Bär, C., and Thum, T. (2019). Circular RNAs: a novel class of functional RNA molecules with a therapeutic perspective. Mol Ther 27, 1350–1363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seetharaman, S., and Etienne-Manneville, S. (2020). Cytoskeletal crosstalk in cell migration. Trends Cell Biol 30, 720–735.

    Article  CAS  PubMed  Google Scholar 

  • Setten, R.L., Rossi, J.J., and Han, S. (2019). The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov 18, 421–446.

    Article  CAS  PubMed  Google Scholar 

  • Shen, S., Yao, T., Xu, Y., Zhang, D., Fan, S., and Ma, J. (2020). CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc. Mol Cancer 19, 151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi, J., Kantoff, P.W., Wooster, R., and Farokhzad, O.C. (2017). Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer 17, 20–37.

    Article  CAS  PubMed  Google Scholar 

  • Singh, S., Narang, A.S., and Mahato, R.I. (2011). Subcellular fate and off-target effects of siRNA, shRNA, and miRNA. Pharm Res 28, 2996–3015.

    Article  CAS  PubMed  Google Scholar 

  • Strieter, E.R., and Korasick, D.A. (2012). Unraveling the complexity of ubiquitin signaling. ACS Chem Biol 7, 52–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., and Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71, 209–249.

    Article  PubMed  Google Scholar 

  • van der Meel, R., Sulheim, E., Shi, Y., Kiessling, F., Mulder, W.J.M., and Lammers, T. (2019). Smart cancer nanomedicine. Nat Nanotechnol 14, 1007–1017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vo, J.N., Cieslik, M., Zhang, Y., Shukla, S., Xiao, L., Zhang, Y., Wu, Y.M., Dhanasekaran, S.M., Engelke, C.G., Cao, X., et al. (2019). The landscape of circular RNA in cancer. Cell 176, 869–881.e13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, L., Long, H., Zheng, Q., Bo, X., Xiao, X., and Li, B. (2019a). Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer 18, 119.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, P., Zheng, H., Zhang, J., Wang, Y., Liu, P., Xuan, X., Li, Q., and Du, Y. (2020). Identification of key gene modules and genes in colorectal cancer by co-expression analysis weighted gene co-expression network analysis. Biosci Rep 40, BSR20202044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, X., Ding, C., and Li, H.B. (2024). The crosstalk between enteric nervous system and immune system in intestinal development, homeostasis and diseases. Sci China Life Sci 67, 41–50.

    Article  PubMed  Google Scholar 

  • Wang, Y., Liu, J., Ma, J., Sun, T., Zhou, Q., Wang, W., Wang, G., Wu, P., Wang, H., Jiang, L., et al. (2019b). Exosomal circRNAs: biogenesis, effect and application in human diseases. Mol Cancer 18, 116.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Yan, Q., Fan, C., Mo, Y., Wang, Y., Li, X., Liao, Q., Guo, C., Li, G., Zeng, Z., et al. (2023). Overview and countermeasures of cancer burden in China. Sci China Life Sci 66, 2515–2526.

    Article  PubMed  Google Scholar 

  • Wu, F., Yang, J., Liu, J., Wang, Y., Mu, J., Zeng, Q., Deng, S., and Zhou, H. (2021). Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Sig Transduct Target Ther 6, 218.

    Article  CAS  Google Scholar 

  • Xia, Y., Lv, J., Jiang, T., Li, B., Li, Y., He, Z., Xuan, Z., Sun, G., Wang, S., Li, Z., et al. (2021). CircFAM73A promotes the cancer stem cell-like properties of gastric cancer through the miR-490-3p/HMGA2 positive feedback loop and HNRNPK-mediated β-catenin stabilization. J Exp Clin Cancer Res 40, 103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao, M.S., Ai, Y., and Wilusz, J.E. (2020). Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol 30, 226–240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie, M., Yu, T., Jing, X., Ma, L., Fan, Y., Yang, F., Ma, P., Jiang, H., Wu, X., Shu, Y., et al. (2020). Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation. Mol Cancer 19, 112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, J., Zhang, G., Luo, X., Wang, D., Zhou, W., Zhang, Y., Zhang, W., Chen, J., Meng, Q., Chen, E., et al. (2021). Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts. Theranostics 11, 2475–2489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan, L., and Chen, Y.G. (2020). Circular RNAs in immune response and viral infection. Trends Biochem Sci 45, 1022–1034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, H., Li, X., Meng, Q., Sun, H., Wu, S., Hu, W., Liu, G., Li, X., Yang, Y., and Chen, R. (2020). CircPTK2 (hsa_circ_0005273) as a novel therapeutic target for metastatic colorectal cancer. Mol Cancer 19, 13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu, Y.Z., Lv, D.J., Wang, C., Song, X.L., Xie, T., Wang, T., Li, Z.M., Guo, J.D., Fu, D.J., Li, K.J., et al. (2022). Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR-653-5p. Mol Cancer 21, 12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng, K., He, B., Yang, B.B., Xu, T., Chen, X., Xu, M., Liu, X., Sun, H., Pan, Y., and Wang, S. (2018). The pro-metastasis effect of circANKS1B in breast cancer. Mol Cancer 17, 160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, M., Wang, X., Yang, N., Zhu, X., Lu, Z., Cai, Y., Li, B., Zhu, Y., Li, X., Wei, Y., et al. (2024). Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks. Sci China Life Sci 67, 132–148.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, X.O., Wang, H.B., Zhang, Y., Lu, X., Chen, L.L., and Yang, L. (2014). Complementary sequence-mediated exon circularization. Cell 159, 134–147.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, W., Cui, Y., Liu, L., Qi, X., Liu, J., Ma, S., Hu, X., Zhang, Z., Wang, Y., Li, H., et al. (2020). Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop. Cell Death Differ 27, 919–933.

    Article  CAS  PubMed  Google Scholar 

  • Zheng, S., Hu, L., Song, Q., Shan, Y., Yin, G., Zhu, H., Kong, W., and Zhou, C. (2021). miR-545 promotes colorectal cancer by inhibiting transferring in the non-normal ferroptosis signaling. Aging 13, 26137–26147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou, X., Li, X., Cheng, Y., Wu, W., Xie, Z., Xi, Q., Han, J., Wu, G., Fang, J., and Feng, Y. (2014). BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells. Nat Commun 5, 4581.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgement

This study was supported by the National Natural Science Foundation of China (81771502, 82302899, 32071349, 81701820), the Natural Science Foundation of Zhejiang Province (LH19H160001, LY20H180014), and the Department of Health of Zhejiang Province (2018KY473, 2018PY025).

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Correspondence to Zhangfa Song.

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Chen, J., Wang, H., Xu, J. et al. CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-023-2514-y

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