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C1QTNF6 Targeted by MiR-184 Regulates the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells

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Abstract

Objective

To seek out the mechanism by which C1QTNF6 mediates lung adenocarcinoma (LUAD).

Methods

Differentially expressed mRNAs and miRNAs in LUAD were analyzed using bioinformatics. In LUAD cells, C1QTNF6 mRNA and miR-184 expression were evaluated with qRT-PCR, and C1QTNF6 protein level was assessed by western blot. Cellular behaviors were assessed by colony formation, CCK-8, Transwell, and wound healing methods. The binding ability of miR-184 to C1QTNF6 was observed by dual-luciferase assay.

Results

High expression of C1QTNF6 in LUAD stimulated cancer cellular behaviors. MiR-184 was lowly expressed in LUAD and downregulated C1QTNF6 expression. MiR-184 restrained LUAD cell processes by targeting C1QTNF6.

Conclusion

MiR-184 repressed LUAD cell processes via mediating C1QTNF6. MiR-184 and C1QTNF6 are expected to be indicators for LUAD treatment.

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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. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians., 68, 394–424.

    Google Scholar 

  2. Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer statistics, 2013. CA: A Cancer Journal for Clinicians, 63, 11–30.

    Google Scholar 

  3. Yang, S., Liu, T., Sun, Y., & Liang, X. (2019). The long noncoding RNA LINC00483 promotes lung adenocarcinoma progression by sponging miR-204-3p. Cellular & Molecular Biology Letters, 24, 70.

    Article  CAS  Google Scholar 

  4. Herbst, R. S., Morgensztern, D., & Boshoff, C. (2018). The biology and management of non-small cell lung cancer. Nature, 553, 446–454.

    Article  CAS  PubMed  Google Scholar 

  5. Hughes, P. E., Caenepeel, S., & Wu, L. C. (2016). Targeted therapy and checkpoint immunotherapy combinations for the treatment of cancer. Trends in Immunology., 37, 462–476.

    Article  CAS  PubMed  Google Scholar 

  6. Lin, J. J., & Shaw, A. T. (2016). Resisting resistance: Targeted therapies in lung cancer. Trends in Cancer., 2, 350–364.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Thomas, A., Liu, S. V., Subramaniam, D. S., & Giaccone, G. (2015). Refining the treatment of NSCLC according to histological and molecular subtypes. Nature reviews. Clinical Oncology, 12, 511–526.

    CAS  PubMed  Google Scholar 

  8. Pakkala, S., & Ramalingam, S. S. (2018). Personalized therapy for lung cancer: striking a moving target. JCI Insight, 3.

  9. Hirsch, F. R., Scagliotti, G. V., Mulshine, J. L., Kwon, R., Curran, W. J., Jr., Wu, Y. L., & Paz-Ares, L. (2017). Lung cancer: Current therapies and new targeted treatments. Lancet (London, England)., 389, 299–311.

    Article  CAS  Google Scholar 

  10. Vargas, A. J., & Harris, C. C. (2016). Biomarker development in the precision medicine era: Lung cancer as a case study. Nature reviews. Cancer, 16, 525–537.

    CAS  PubMed  Google Scholar 

  11. Stroikova, V., Fischer, A., Bockstahler, M., Muller, A. M., Katus, H. A., & Kaya, Z. (2019). Adiponectin deficiency has no effect in murine autoimmune myocarditis. Cytokine, 116, 139–149.

    Article  CAS  PubMed  Google Scholar 

  12. Le Poole, I. C., & Luiten, R. M. (2008). Autoimmune etiology of generalized vitiligo. Current Directions in Autoimmunity, 10, 227–243.

    Article  PubMed  Google Scholar 

  13. Qu, H. X., Cui, L., Meng, X. Y., Wang, Z. J., Cui, Y. X., Yu, Y. P., Wang, D., & Jiang, X. J. (2019). C1QTNF6 is overexpressed in gastric carcinoma and contributes to the proliferation and migration of gastric carcinoma cells. International Journal of Molecular Medicine, 43, 621–629.

    CAS  PubMed  Google Scholar 

  14. Han, M., Wang, B., Zhu, M., & Zhang, Y. (2019). C1QTNF6 as a novel biomarker regulates cellular behaviors in A549 cells and exacerbates the outcome of lung adenocarcinoma patients. In vitro cellular & developmental biology. Animal, 55, 614–621.

    CAS  Google Scholar 

  15. Lin, W., Chen, X., Chen, T., Liu, J., Ye, Y., Chen, L., Qiu, X., Chia-Hsien Cheng, J., Zhang, L., Wu, J., & Qiu, S. (2020). C1QTNF6 as a novel diagnostic and prognostic biomarker for clear cell renal cell carcinoma. DNA and Cell Biology, 39, 1000–1011.

    Article  CAS  PubMed  Google Scholar 

  16. Wang, C., Gao, C., Zhuang, J. L., Ding, C., & Wang, Y. (2012). A combined approach identifies three mRNAs that are down-regulated by microRNA-29b and promote invasion ability in the breast cancer cell line MCF-7. Journal of Cancer Research and Clinical Oncology, 138, 2127–2136.

    Article  CAS  PubMed  Google Scholar 

  17. Zhou, Y., Li, S., Li, J., Wang, D., & Li, Q. (2017). Effect of microRNA-135a on cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer. Cellular Physiology and Biochemistry, 42, 1431–1446.

    Article  CAS  PubMed  Google Scholar 

  18. Li, W., Li, X., Li, X., Li, M., Yang, P., Wang, X., Li, L., & Yang, B. (2020). Lamin B1 overexpresses in lung adenocarcinoma and promotes proliferation in lung cancer cells via AKT pathway. Oncotargets and Therapy, 13, 3129–3139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xu, L., Sun, H. B., Xu, Z. N., Han, X. L., Yin, Y. Y., Zheng, Y., Zhao, Y., & Wang, Z. X. (2019). MicroRNA-218 regulates the epithelial-to-mesenchymal transition and the PI3K/Akt signaling pathway to suppress lung adenocarcinoma progression by directly targeting BMI-1. European Review for Medical and Pharmacological Sciences, 23, 7978–7988.

    CAS  PubMed  Google Scholar 

  20. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, J., Yao, S., Diao, Y., Geng, Y., Bi, Y., & Liu, G. (2020). miR-15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2. Thoracic Cancer, 11, 1396–1405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhao, H., Zheng, C., Wang, Y., Hou, K., Yang, X., Cheng, Y., Che, X., Xie, S., Wang, S., Zhang, T., Kang, J., Liu, Y., Pan, D., Qu, X., Hu, X., & Fan, Y. (2020). miR-1323 promotes cell migration in lung adenocarcinoma by targeting Cbl-b and is an early prognostic biomarker. Frontiers in Oncology, 10, 181.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yu, C., Tian, F., Liu, J., Su, M., Wu, M., Zhu, X., & Qian, W. (2019). Circular RNA cMras inhibits lung adenocarcinoma progression via modulating miR-567/PTPRG regulatory pathway. Cell Proliferation, 52, 12–610.

    Article  Google Scholar 

  24. Takeuchi, T., Adachi, Y., & Nagayama, T. (2011). Expression of a secretory protein C1qTNF6, a C1qTNF family member, in hepatocellular carcinoma. Analytical Cellular Pathology (Amsterdam), 34, 113–121.

    Article  CAS  Google Scholar 

  25. Zhang, H. J., Tao, J., Sheng, L., Hu, X., Rong, R. M., Xu, M., & Zhu, T. Y. (2016). Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway. OncoTargets and Therapy., 9, 1801–1812.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rahimian, P., & He, J. J. (2016). HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression. Journal of Neuroinflammation, 13, 247.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Huntzinger, E., & Izaurralde, E. (2011). Gene silencing by microRNAs: Contributions of translational repression and mRNA decay. Nature Reviews Genetics, 12, 99–110.

    Article  CAS  PubMed  Google Scholar 

  28. Cheng, Z., Wang, H. Z., Li, X., Wu, Z., Han, Y., Li, Y., Chen, G., Xie, X., Huang, Y., Du, Z., & Zhou, Y. (2015). MicroRNA-184 inhibits cell proliferation and invasion, and specifically targets TNFAIP2 in Glioma. Journal of Experimental & Clinical Cancer Research, 34, 27.

    Article  CAS  Google Scholar 

  29. Gao, B., Gao, K., Li, L., Huang, Z., & Lin, L. (2014). miR-184 functions as an oncogenic regulator in hepatocellular carcinoma (HCC). Biomedicine & Pharmacotherapy, 68, 143–148.

    Article  CAS  Google Scholar 

  30. Su, Z., Chen, D., Li, Y., Zhang, E., Yu, Z., Chen, T., Jiang, Z., Ni, L., Yang, S., Gui, Y., Ye, J., & Lai, Y. (2015). microRNA-184 functions as tumor suppressor in renal cell carcinoma. Experimental and Therapeutic Medicine, 9, 961–966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wan, X., Zheng, C., & Dong, L. (2019). Inhibition of CTRP6 prevented survival and migration in hepatocellular carcinoma through inactivating the AKT signaling pathway. Journal of Cellular Biochemistry., 120, 17059–17066.

    Article  CAS  PubMed  Google Scholar 

  32. Dong, X., Hu, H., Fang, Z., Cui, J., & Liu, F. (2018). CTRP6 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration. Biomedicine & Pharmacotherapy, 103, 844–850.

    Article  CAS  Google Scholar 

  33. Hamamdzic, D., Fenning, R. S., Patel, D., Mohler, E. R., 3rd., Orlova, K. A., Wright, A. C., Llano, R., Keane, M. G., Shannon, R. P., Birnbaum, M. J., & Wilensky, R. L. (2010). Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease. American Journal of Physiology Heart and Circulatory Physiology., 299, H699-706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Derrick, T., Last, A. R., Burr, S. E., Roberts, C. H., Nabicassa, M., Cassama, E., Bailey, R. L., Mabey, D. C., Burton, M. J., & Holland, M. J. (2016). Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection. BMC Infectious Diseases., 16, 60.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Qin, C. Z., Lou, X. Y., Lv, Q. L., Cheng, L., Wu, N. Y., Hu, L., & Zhou, H. H. (2015). MicroRNA-184 acts as a potential diagnostic and prognostic marker in epithelial ovarian cancer and regulates cell proliferation, apoptosis and inflammation. Die Pharmazie., 70, 668–673.

    CAS  PubMed  Google Scholar 

  36. Foley, N. H., Bray, I. M., Tivnan, A., Bryan, K., Murphy, D. M., Buckley, P. G., Ryan, J., O’Meara, A., O’Sullivan, M., & Stallings, R. L. (2010). MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2. Molecular Cancer, 9, 83.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Liu, C., Teng, Z. Q., Santistevan, N. J., Szulwach, K. E., Guo, W., Jin, P., & Zhao, X. (2010). Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell, 6, 433–444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Yu, J., Ryan, D. G., Getsios, S., Oliveira-Fernandes, M., Fatima, A., & Lavker, R. M. (2008). MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia. Proceedings of the National Academy of Sciences of the United States of America., 105, 19300–19305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Weitzel, R. P., Lesniewski, M. L., Haviernik, P., Kadereit, S., Leahy, P., Greco, N. J., & Laughlin, M. J. (2009). microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood, 113, 6648–6657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Misono, S., Seki, N., Mizuno, K., Yamada, Y., Uchida, A., Sanada, H., Moriya, S., Kikkawa, N., Kumamoto, T., Suetsugu, T., & Inoue, H. (2019). Molecular pathogenesis of gene regulation by the mir-150 duplex: miR-150–3p regulates TNS4 in lung adenocarcinoma. Cancers., 11, 601.

    Article  CAS  PubMed Central  Google Scholar 

  41. Jiang, H., Xu, S., & Chen, C. (2020). A ten-gene signature-based risk assessment model predicts the prognosis of lung adenocarcinoma. BMC Cancer, 20, 782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang, M., Lan, X., & Chen, Y. (2021). MiR-133b suppresses the proliferation, migration and invasion of lung adenocarcinoma cells by targeting SKA3. Cancer Biology & Therapy., 22, 571–578.

    Article  CAS  Google Scholar 

  43. Han, J., Rong, Y., & Gao, X. (2021). Multiomic analysis of the function of SPOCK1 across cancers: An integrated bioinformatics approach. The Journal of International Medical Research., 49, 300060520962659.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yunping Lu.

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Rao, X., Lu, Y. C1QTNF6 Targeted by MiR-184 Regulates the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells. Mol Biotechnol 64, 1279–1287 (2022). https://doi.org/10.1007/s12033-022-00495-z

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  • DOI: https://doi.org/10.1007/s12033-022-00495-z

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