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ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting

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Abstract

Colorectal cancer (CRC) belongs to one of gastric cancers that half of cases will develop metastasis, causing higher mortality or chemotherapy resistance. In the present study, the long noncoding RNA zinc finger antisense 1 (ZFAS1) was proved to have high expression level in CRC samples and in advanced stages. Additionally, it also indicated that p53 status is associated with ZFAS1 expression. Silencing ZFAS1 reduced both migration and invasion ability of DLD-1 and HCT-116 cells, which is relevant to the EMT process. In addition, it was confirmed that miR-34b, a tumor suppressor miRNA directly targeted ZFAS1 3′ untranslated region (3′UTR) and inhibited ZFAS1 expression. Furthermore, miR-34b partially reversed the effect of ZFAS1 on migration and invasion ability in DLD-1 cells. Meanwhile, p53 status changes by overexpression vectors or siRNA turbulent ZFAS1 expression. Besides, it was found that in most cases, the oncogene SOX4 was directly targeted by miR-34b and positive correlated to ZFAS1 expression. Silencing ZFAS1 induced SOX4 expression in DLD-1 cells. Our data demonstrated the functions and mechanisms of ZFAS1 in CRC metastasis, illustrating miR-34b directly targets ZFAS1 and inhibits metastasis ability of CRC cells. SOX4 is also the direct downstream target of miR-34b, and silencing ZFAS1 can inhibit SOX4 though modulating miR-34b.

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Data availability

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

References

  1. Oga, T., Yamashita, Y., Soda, M., Kojima, S., Ueno, T., & Kawazu, M., et al. (2019). Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes. Cancer Science, 110(9), 2973–2981

    Article  CAS  Google Scholar 

  2. Janssen, E., Subtil, B., de la Jara Ortiz, F., Verheul, H. M. W., & Tauriello, D. V. F. (2020). Combinatorial Immunotherapies for metastatic colorectal cancer. Cancers (Basel)., 12, 1875

    Article  CAS  Google Scholar 

  3. Kanwal, S., Guo, X., Ward, C., Volpe, G., Qin, B., & Esteban, M. A. et al. (2020). Role of long non-coding RNAs in reprogramming to induced pluripotency. Genomics Proteomics Bioinformatics, 18(1), 16–25.

    Article  Google Scholar 

  4. Li, Z., & Sun, X. (2020). Non-coding RNAs operate in the crosstalk between cancer metabolic reprogramming and metastasis. Frontiers in Oncology, 10, 810

    Article  Google Scholar 

  5. Pal, S., Garg, M., & Pandey, A. K. (2020). Deciphering the mounting complexity of the p53 regulatory network in correlation to long non-coding RNAs (lncRNAs) in ovarian. Cancer Cells., 9(3), 527

    CAS  Google Scholar 

  6. Talebian, S., Daghagh, H., Yousefi, B., Ozkul, Y., Ilkhani, K., & Seif, F., et al. (2020). The role of epigenetics and non-coding RNAs in autophagy: A new perspective for thorough understanding. Mechanics of Ageing and Development, 190, 111309

    Article  CAS  Google Scholar 

  7. Askarian-Amiri, M. E., Crawford, J., French, J. D., Smart, C. E., Smith, M. A., & Clark, M. B., et al. (2011). SNORD-host RNA Zfas1 is a regulator of mammary development and a potential marker for breast cancer. RNA, 17(5), 878–891

    Article  CAS  Google Scholar 

  8. Guo, H., Wu, L., Zhao, P., & Feng, A. (2017). Overexpression of long non-coding RNA zinc finger antisense 1 in acute myeloid leukemia cell lines influences cell growth and apoptosis. Experimental and Therapeutic Medicine, 14(1), 647–651

    Article  CAS  Google Scholar 

  9. Li, T., Xie, J., Shen, C., Cheng, D., Shi, Y., & Wu, Z., et al. (2015). Amplification of long noncoding RNA ZFAS1 promotes metastasis in hepatocellular carcinoma. Cancer Research, 75(15), 3181–3191

    Article  CAS  Google Scholar 

  10. Shi, L., Hong, X., Ba, L., He, X., Xiong, Y., & Ding, Q., et al. (2019). Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression. Cell Death and Disease, 10(3), 150

    Article  Google Scholar 

  11. Tian, F. M., Meng, F. Q., & Wang, X. B. (2016). Overexpression of long-noncoding RNA ZFAS1 decreases survival in human NSCLC patients. European Review for Medical Pharmacological Sciences, 20(24), 5126–5131

    PubMed  Google Scholar 

  12. Ye, D., Jian, W., Feng, J., & Liao, X. (2018). Role of long noncoding RNA ZFAS1 in proliferation, apoptosis and migration of chondrocytes in osteoarthritis. Biomedicine and Pharmacotherapy, 104, 825–831

    Article  CAS  Google Scholar 

  13. Chen, X., Zeng, K., Xu, M., Hu, X., Liu, X., & Xu, T., et al. (2018). SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis. Cell Death and Disease, 9(10), 982

    Article  Google Scholar 

  14. Nie, F., Yu, X., Huang, M., Wang, Y., Xie, M., & Ma, H., et al. (2017). Long noncoding RNA ZFAS1 promotes gastric cancer cells proliferation by epigenetically repressing KLF2 and NKD2 expression. Oncotarget, 8(24), 38227–38238

    Article  Google Scholar 

  15. Rokavec, M., Li, H., Jiang, L., & Hermeking, H. (2014). The p53/miR-34 axis in development and disease. Journal of Molecular Cell Biology, 6(3), 214–230

    Article  CAS  Google Scholar 

  16. Jiang, L., & Hermeking, H. (2017). miR-34a and miR-34b/c suppress intestinal tumorigenesis. Cancer Research, 77(10), 2746–2758

    Article  CAS  Google Scholar 

  17. Siemens, H., Neumann, J., Jackstadt, R., Mansmann, U., Horst, D., & Kirchner, T., et al. (2013). Detection of miR-34a promoter methylation in combination with elevated expression of c-Met and beta-catenin predicts distant metastasis of colon cancer. Clinical Cancer Research, 19(3), 710–720

    Article  CAS  Google Scholar 

  18. Wang, Q., Liu, D., Wang, K., Li, C., Han, X., & Zhang, Z., et al. (2019). Hypermethylation of miR-34b/c is associated with early clinical stages and tumor differentiation in Kazakh patients with esophageal squamous cell carcinoma. International Journal of Clinical and Experimental Pathology, 12(8), 3119–3127

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Cancer Genome Atlas Network. (2012). Comprehensive molecular characterization of human colon and rectal cancer. Nature, 487(7407), 330–337

    Article  Google Scholar 

  20. Brenner, H., Kloor, M., & Pox, C. P. (2014). Colorectal cancer. Lancet., 383(9927), 1490–1502

    Article  Google Scholar 

  21. Xiong, S., Hu, M., Li, C., Zhou, X., & Chen, H. (2019). Role of miR34 in gastric cancer: From bench to bedside (Review). Oncology Reports, 42(5), 1635–1646

    CAS  PubMed  Google Scholar 

  22. Luo, C., Quan, Z., Zhong, B., Zhang, M., Zhou, B., & Wang, S., et al. (2020). lncRNA XIST promotes glioma proliferation and metastasis through miR-133a/SOX4. Experimental and Therapeutic Medicine, 19, 1641–1648

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tsai, C. N., Yu, S. C., Lee, C. W., Pang, J. S., Wu, C. H., & Lin, S. E., et al. (2020). SOX4 activates CXCL12 in hepatocellular carcinoma cells to modulate endothelial cell migration and angiogenesis in vivo. Oncogene, 39(24), 4695–4710

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the scientific research projects of Sichuan Medical Association [S17076].

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Authors and Affiliations

  1. Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646099, PR China

    Hong Deng, Mingming Wang, Qin Xu & Hui Yao

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  1. Hong Deng
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  2. Mingming Wang
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  3. Qin Xu
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  4. Hui Yao
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Contributions

HD and HY contributed to the study conception and design. Material preparation, data collection and analysis were performed by HD, MW, and QX. The first draft of the manuscript was written by HD and HY, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hui Yao.

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Deng, H., Wang, M., Xu, Q. et al. ZFAS1 Promotes Colorectal Cancer Metastasis Through Modulating miR-34b/SOX4 Targeting. Cell Biochem Biophys 79, 387–396 (2021). https://doi.org/10.1007/s12013-021-00976-z

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  • DOI: https://doi.org/10.1007/s12013-021-00976-z

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