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Let-7c-5p Restrains Cell Growth and Induces Apoptosis of Lung Adenocarcinoma Cells via Targeting ESPL1

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Abstract

Lung adenocarcinoma (LUAD) is a predominant malignancy, and its high mortality prompts us to incessantly probe the relevant targeted treatment. This work intended to study the molecular mechanism of ESPL1 in LUAD. Bioinformatics analysis was performed for pan-cancer and prognosis analysis as well as target gene prediction. Expression of ESPL1 mRNA and let-7c-5p was determined via qRT-PCR, and western blot was employed to detect protein level of ESPL1. Dual-luciferase reporter gene method verified the interaction between ESPL1 and let-7c-5p. Thereafter, CCK-8, wound healing, Transwell, and flow cytometry assays were utilized to investigate proliferation, migration, and apoptosis of LUAD cells. The results revealed that ESPL1 was upregulated in LUAD, which was associated with poor prognosis. Overexpressed ESPL1 promoted LUAD cells to invade, proliferate, and migrate. Furthermore, ESPL1 was a target gene of let-7c-5p. Let-7c-5p was downregulated in LUAD cells, and played a suppressive role in LUAD malignant development, while reversed by ESPL1. Taken together, it was posited that let-7c-5p/ESPL1 may be underlying therapeutic targets of LUAD.

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Data Availability

The data used to support the findings of this study are included within the article. The data and materials in the current study are available from the corresponding author on reasonable request.

References

  1. Henley, S. J., Ward, E. M., Scott, S., Ma, J., Anderson, R. N., Firth, A.U., Thomas, C.C., Islami, F., Weir, H. K., Lewis, D.R., Sherman, R. L., Wu, M., Benard, V. B., Richardson, L. C., Jemal, A., Cronin, K., Kohler, B. A. (2020). Annual report to the nation on the status of cancer, part I: National cancer statistics. Cancer, 126, 2225–2249. https://doi.org/10.1002/cncr.32802

    Article  PubMed  Google Scholar 

  2. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., Jemal, A. (2015). Global cancer statistics, 2012. CA: A Cancer Journal for Clinicians, 65, 87–108. https://doi.org/10.3322/caac.21262

    Article  Google Scholar 

  3. Blandin Knight, S., Crosbie, P. A., Balata, H., Chudziak, J., Hussell, T., Dive, C. (2017). Progress and prospects of early detection in lung cancer. Open Biology. https://doi.org/10.1098/rsob.170070

    Article  PubMed  PubMed Central  Google Scholar 

  4. Pan, Z., Liu, H., & Chen, J. (2022). Lung cancer stem-like cells and drug resistance. Zhongguo fei ai za zhi = Chinese Journal of Lung Cancer, 25, 111–117. https://doi.org/10.3779/j.issn.1009-3419.2022.102.02

    Article  PubMed  Google Scholar 

  5. Heng, W. S., Gosens, R., & Kruyt, F. A. E. (2019). Lung cancer stem cells: Origin, features, maintenance mechanisms and therapeutic targeting. Biochemical pharmacology, 160, 121–133. https://doi.org/10.1016/j.bcp.2018.12.010

    Article  PubMed  CAS  Google Scholar 

  6. Nasmyth, K., & Haering, C. H. (2009). Cohesin: Its roles and mechanisms. Annual Review of Genetics, 43, 525–558. https://doi.org/10.1146/annurev-genet-102108-134233

    Article  PubMed  CAS  Google Scholar 

  7. Uhlmann, F. (2001). Secured cutting: Controlling separase at the metaphase to anaphase transition. EMBO Reports, 2, 487–492. https://doi.org/10.1093/embo-reports/kve113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Mukherjee, M., Ge, G., Zhang, N., Edwards, D. G., Sumazin, P., Sharan, S. K., Rao, P. H., Medina, D., Pati, D. (2014). MMTV-Espl1 transgenic mice develop aneuploid, estrogen receptor alpha (ERalpha)-positive mammary adenocarcinomas. Oncogene, 33, 5511–5522. https://doi.org/10.1038/onc.2013.493

    Article  PubMed  CAS  Google Scholar 

  9. Tan, K. S., Armugam, A., Sepramaniam, S., Lim, K. Y., Setyowati, K. D., Wang, C. W., Jeyaseelan, K. (2009). Expression profile of MicroRNAs in young stroke patients. PLoS ONE, 4, e7689. https://doi.org/10.1371/journal.pone.0007689

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Li, J., Wang, Y., Song, Y., Fu, Z., & Yu, W. (2014). miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells. Molecular Cancer, 13, 193. https://doi.org/10.1186/1476-4598-13-193

    Article  PubMed  PubMed Central  Google Scholar 

  11. An, J. C., Shi, H. B., Hao, W. B., Zhu, K., & Ma, B. (2019). miR-944 inhibits lung adenocarcinoma tumorigenesis by targeting STAT1 interaction. Oncology Letters, 17, 3790–3798. https://doi.org/10.3892/ol.2019.10045

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Zhang, X., Zhu, J., Xing, R., Tie, Y., Fu, H., Zheng, X., Yu, B. (2012). miR-513a-3p sensitizes human lung adenocarcinoma cells to chemotherapy by targeting GSTP1. Lung Cancer, 77, 488–494. https://doi.org/10.1016/j.lungcan.2012.05.107

    Article  PubMed  Google Scholar 

  13. Roush, S., & Slack, F. J. (2008). The let-7 family of microRNAs. Trends in Cell Biology, 18, 505–516. https://doi.org/10.1016/j.tcb.2008.07.007

    Article  PubMed  CAS  Google Scholar 

  14. Meneely, P. M., & Herman, R. K. (1979). Lethals, steriles and deficiencies in a region of the X chromosome of Caenorhabditis elegans. Genetics, 92, 99–115. https://doi.org/10.1093/genetics/92.1.99

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Reinhart, B. J., Slack, F. J., Basson, M., Pasquinelli, A. E., Bettinger, J. C., Rougvie, A. E., Horvitz, H. R., Ruvkun, G. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 403, 901–906. https://doi.org/10.1038/35002607

    Article  PubMed  CAS  Google Scholar 

  16. Chen, S., Xie, C., & Hu, X. (2019). lncRNA SNHG6 functions as a ceRNA to up-regulate c-Myc expression via sponging let-7c-5p in hepatocellular carcinoma. Biochemical and Biophysical Research Communications, 519, 901–908. https://doi.org/10.1016/j.bbrc.2019.09.091

    Article  PubMed  CAS  Google Scholar 

  17. Jilek, J. L., Tu, M. J., Zhang, C., & Yu, A. M. (2020). Pharmacokinetic and pharmacodynamic factors contribute to synergism between Let-7c-5p and 5-fluorouracil in inhibiting hepatocellular carcinoma cell viability. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 48, 1257–1263. https://doi.org/10.1124/dmd.120.000207

    Article  CAS  Google Scholar 

  18. Jilek, J. L., Zhang, Q. Y., Tu, M. J., Ho, P. Y., Duan, Z., Qiu, J. X., Yu, A. M. (2019). Bioengineered Let-7c inhibits orthotopic hepatocellular carcinoma and improves overall survival with minimal immunogenicity. Molecular Therapy-Nucleic Acids, 14, 498–508. https://doi.org/10.1016/j.omtn.2019.01.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Zhao, B., Han, H., Chen, J., Zhang, Z., Li, S., Fang, F., Zheng, Q., Ma, Y., Zhang, J., Wu, N., Yang, Y. (2014). MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer Letters, 342, 43–51. https://doi.org/10.1016/j.canlet.2013.08.030

    Article  PubMed  CAS  Google Scholar 

  20. Wang, L., Xiao, X., & Du, H. (2022). The regulation of let-7c-5p on the biological characteristics of lung adenocarcinoma cells by targeting AURKB. Molecular Biotechnology, 64, 526–534. https://doi.org/10.1007/s12033-021-00446-0

    Article  PubMed  CAS  Google Scholar 

  21. Wang, Y., Zhou, Z., Chen, L., Li, Y., Zhou, Z., Chu, X. (2021). Identification of key genes and biological pathways in lung adenocarcinoma via bioinformatics analysis. Molecular and Cellular Biochemistry, 476, 931–939. https://doi.org/10.1007/s11010-020-03959-5

    Article  PubMed  CAS  Google Scholar 

  22. Travis, W. D. (2011). Pathology of lung cancer. Clinics in Chest Medicine, 32, 669–692. https://doi.org/10.1016/j.ccm.2011.08.005

    Article  PubMed  Google Scholar 

  23. Mukherjee, M., Ge, G., Zhang, N., Huang, E., Nakamura, L. V., Minor, M., Fofanov, V., Rao, P. H., Herron, A., Pati, D. (2011). Separase loss of function cooperates with the loss of p53 in the initiation and progression of T-and B-cell lymphoma, leukemia and aneuploidy in mice. PLoS ONE, 6, e22167. https://doi.org/10.1371/journal.pone.0022167

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Rao, Z. L., Dong, J., Zhu, Y. Y., Chen, J., You, J., Zheng, Q., Jiang, J. J. (2013). Hepatitis B surface antigen affects the expression of lipid metabolism-related genes in HepG2 cells. Zhonghua Gan Zang Bing Za Zhi, 21, 624–630. https://doi.org/10.3760/cma.j.issn.1007-3418.2013.08.014

    Article  PubMed  CAS  Google Scholar 

  25. Finetti, P., Guille, A., Adelaide, J., Birnbaum, D., Chaffanet, M,. Bertucci, F. (2014). ESPL1 is a candidate oncogene of luminal B breast cancers. Breast Cancer Research and Treatment, 147, 51–59. https://doi.org/10.1007/s10549-014-3070-z

    Article  PubMed  CAS  Google Scholar 

  26. Sak, A., Fegers, I., Groneberg, M., & Stuschke, M. (2008). Effect of separase depletion on ionizing radiation-induced cell cycle checkpoints and survival in human lung cancer cell lines. Cell Proliferation, 41, 660–670. https://doi.org/10.1111/j.1365-2184.2008.00540.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Fu, X., Mao, X., Wang, Y., Ding, X., & Li, Y. (2017). Let-7c-5p inhibits cell proliferation and induces cell apoptosis by targeting ERCC6 in breast cancer. Oncology Reports, 38, 1851–1856. https://doi.org/10.3892/or.2017.5839

    Article  PubMed  CAS  Google Scholar 

  28. Nwaeburu, C. C., Bauer, N., Zhao, Z., Abukiwan, A., Gladkich, J., Benner, A., Herr, I. (2016). Up-regulation of microRNA let-7c by quercetin inhibits pancreatic cancer progression by activation of Numbl. Oncotarget, 7, 58367–58380. https://doi.org/10.18632/oncotarget.11122

    Article  PubMed  PubMed Central  Google Scholar 

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Liu, X., Zeng, W., Zheng, D. et al. Let-7c-5p Restrains Cell Growth and Induces Apoptosis of Lung Adenocarcinoma Cells via Targeting ESPL1. Mol Biotechnol 64, 1367–1375 (2022). https://doi.org/10.1007/s12033-022-00511-2

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