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MiRNA-30a-5p/VCAN Arrests Tumor Metastasis via Modulating the Adhesion of Lung Adenocarcinoma Cells

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Abstract

Previous research indicated that the dysregulation of miRNA-30a-5p has a correlation with cell metastasis of lung adenocarcinoma (LUAD). But the study about the molecular regulatory mechanism of miRNA-30a-5p in LUAD cell metastasis is limited. Thus, we discussed the mechanism of miRNA-30a-5p and its biological function in LUAD cells. By utilizing bioinformatics analysis, how miRNA-30a-5p was expressed in LUAD tissue was determined and its downstream target genes were predicted. The signaling pathways where these target genes enriched were analyzed. Several in vitro experiments were applied for cell function detection: dual-luciferase assay for validating the targeting relationship between miRNA-30a-5p and its target gene; quantitative real-time polymerase chain reaction for testing the expression of miRNA-30a-5p and its target gene in LUAD cells; MTT, transwell, cell adhesion, flow cytometry and immunofluorescence assays for examining the capabilities of LUAD cells to proliferate, migrate, invade, adhere, apoptosis and epithelial-mesenchymal transition (EMT) effect; Western blot for determining the expression of adhesion-related proteins and EMT-related proteins. Down-regulated miRNA-30a-5p was discovered in LUAD cells, but on the contrary, VCAN was upregulated. MiRNA-30a-5p overexpression notably repressed the virulent progression of LUAD cells. Besides, dual-luciferase assay validated the targeting relationship between miRNA-30a-5p and VCAN. MiRNA-30a-5p, by negatively regulating VCAN, was capable of hindering LUAD cell proliferation, migration, invasion, adhesion, viability and EMT. It was illustrated that miRNA-30a-5p could downregulate VCAN to retard the malignant progression of LUAD cells, which provides novel insights into LUAD pathogenesis, suggesting that miRNA-30a-5p/VCAN axis can be a promising anti-cancer target for LUAD.

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Data Availability

The datasets generated and analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

  1. Jones, G. S., & Baldwin, D. R. (2018). Recent advances in the management of lung cancer. Clinical Medicine (London, England), 18, s41–s46. https://doi.org/10.7861/clinmedicine.18-2-s41

    Article  PubMed  Google Scholar 

  2. Chen, Z., Fillmore, C. M., Hammerman, P. S., Kim, C. F., & Wong, K. K. (2014). Non-small-cell lung cancers: A heterogeneous set of diseases. Nature Reviews Cancer, 14, 535–546. https://doi.org/10.1038/nrc3775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wang, C., Wu, Y., Shao, J., Liu, D., & Li, W. (2020). Clinicopathological variables influencing overall survival, recurrence and post-recurrence survival in resected stage I non-small-cell lung cancer. BMC Cancer, 20, 150. https://doi.org/10.1186/s12885-020-6621-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chun, Y. S., et al. (2019). Deleterious effect of RAS and evolutionary high-risk TP53 double mutation in colorectal liver metastases. Annals of Surgery, 269, 917–923. https://doi.org/10.1097/SLA.0000000000002450

    Article  PubMed  Google Scholar 

  5. Erdogan, B., & Webb, D. J. (2017). Cancer-associated fibroblasts modulate growth factor signaling and extracellular matrix remodeling to regulate tumor metastasis. Biochemical Society Transactions, 45, 229–236. https://doi.org/10.1042/BST20160387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Le Noci, V., et al. (2018). Modulation of pulmonary microbiota by antibiotic or probiotic aerosol therapy: A strategy to promote immunosurveillance against lung metastases. Cell Reports, 24, 3528–3538. https://doi.org/10.1016/j.celrep.2018.08.090

    Article  CAS  PubMed  Google Scholar 

  7. Zeng, Y., et al. (2015). MUC1 predicts colorectal cancer metastasis: A systematic review and meta-analysis of case controlled studies. PLoS One, 10, e0138049. https://doi.org/10.1371/journal.pone.0138049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ji, Z. H., Zhang, Y., & Li, Y. (2021). Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review. Journal Gastrointestinal Oncology, 12, S70–S78. https://doi.org/10.21037/jgo-20-262

    Article  Google Scholar 

  9. Welter, S., Gupta, V., & Kyritsis, I. (2021). Lymphadenectomy in pulmonary metastasectomy. J Thorac Dis, 13, 2611–2617. https://doi.org/10.21037/jtd.2020.04.09

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hugenschmidt, H. et al (2021) Preoperative CTC-detection by CellSearch((R)) is associated with early distant metastasis and impaired survival in resected pancreatic cancer. Cancers (Basel), 13, 485. https://doi.org/10.3390/cancers13030485.

  11. Zhang, D., et al. (2020). VCAM1 Promotes tumor cell invasion and metastasis by inducing EMT and transendothelial migration in colorectal cancer. Frontiers in Oncology, 10, 1066. https://doi.org/10.3389/fonc.2020.01066

    Article  PubMed  PubMed Central  Google Scholar 

  12. Edwards, I. J. (2012). Proteoglycans in prostate cancer. Nature Reviews. Urology, 9, 196–206. https://doi.org/10.1038/nrurol.2012.19

    Article  CAS  PubMed  Google Scholar 

  13. Ricciardelli, C., Sakko, A. J., Ween, M. P., Russell, D. L., & Horsfall, D. J. (2009). The biological role and regulation of versican levels in cancer. Cancer and Metastasis Reviews, 28, 233–245. https://doi.org/10.1007/s10555-009-9182-y

    Article  PubMed  Google Scholar 

  14. Zhang, Q., et al. (2021). Upregulation of Versican associated with tumor progression, metastasis, and poor prognosis in bladder carcinoma. BioMed Research International, 2021, 6949864. https://doi.org/10.1155/2021/6949864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang, Y., et al. (2019). Enhanced PAPSS2/VCAN sulfation axis is essential for snail-mediated breast cancer cell migration and metastasis. Cell Death and Differentiation, 26, 565–579. https://doi.org/10.1038/s41418-018-0147-y

    Article  CAS  PubMed  Google Scholar 

  16. Cen, S. Y., et al. (2020). A microRNA disease signature associated with lymph node metastasis of lung adenocarcinoma. Mathematical Biosciences and Engineering, 17, 2557–2568. https://doi.org/10.3934/mbe.2020140

    Article  PubMed  Google Scholar 

  17. Jing, P., et al. (2020). miR-24-3p/KLF8 Signaling axis contributes to LUAD metastasis by regulating EMT. Journal of Immunology Research, 2020, 4036047. https://doi.org/10.1155/2020/4036047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun, L., et al. (2019). miR-302a inhibits metastasis and cetuximab resistance in colorectal cancer by targeting NFIB and CD44. Theranostics, 9, 8409–8425. https://doi.org/10.7150/thno.36605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li, Q., et al. (2018). Exosomal miR-21-5p derived from gastric cancer promotes peritoneal metastasis via mesothelial-to-mesenchymal transition. Cell Death & Disease, 9, 854. https://doi.org/10.1038/s41419-018-0928-8

    Article  CAS  Google Scholar 

  20. Ren, L., et al. (2019). MiR-454-3p-mediated Wnt/beta-catenin signaling antagonists suppression promotes breast cancer metastasis. Theranostics, 9, 449–465. https://doi.org/10.7150/thno.29055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chen, C., Tang, J., Xu, S., Zhang, W., & Jiang, H. (2020). miR-30a-5p inhibits proliferation and migration of lung squamous cell carcinoma cells by targeting FOXD1. BioMed Research International, 2020, 2547902. https://doi.org/10.1155/2020/2547902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wu, W., et al. (2020). LncRNA DLEU2 accelerates the tumorigenesis and invasion of non-small cell lung cancer by sponging miR-30a-5p. Journal of Cellular and Molecular Medicine, 24, 441–450. https://doi.org/10.1111/jcmm.14749

    Article  CAS  PubMed  Google Scholar 

  23. Xiong, J., Wei, B., Ye, Q., & Liu, W. (2019). MiR-30a-5p/UBE3C axis regulates breast cancer cell proliferation and migration. Biochemical and Biophysical Research Communications, 516, 1013–1018. https://doi.org/10.1016/j.bbrc.2016.03.069

    Article  CAS  PubMed  Google Scholar 

  24. Huang, X., Wang, L., Liu, W., & Li, F. (2019). MicroRNA-497-5p inhibits proliferation and invasion of non-small cell lung cancer by regulating FGF2. Oncology Letters, 17, 3425–3431. https://doi.org/10.3892/ol.2019.9954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wan, J., & Wu, W. (2016). Hyperthermia induced HIF-1a expression of lung cancer through AKT and ERK signaling pathways. Journal of Experimental & Clinical Cancer Research, 35, 119. https://doi.org/10.1186/s13046-016-0399-7

    Article  CAS  Google Scholar 

  26. Chen, S., et al. (2021). Forkhead box D1 promotes EMT and chemoresistance by upregulating lncRNA CYTOR in oral squamous cell carcinoma. Cancer Letters, 503, 43–53. https://doi.org/10.1016/j.canlet.2020.11.046

    Article  CAS  PubMed  Google Scholar 

  27. Fu, Q., et al. (2018). Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer. Oncogene, 37, 6105–6118. https://doi.org/10.1038/s41388-018-0391-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Deng, F., Xu, Z., Zhou, J., Zhang, R., & Gong, X. (2021). ANLN regulated by miR-30a-5p mediates malignant progression of lung adenocarcinoma. Computational and Mathematical Methods in Medicine, 2021, 9549287. https://doi.org/10.1155/2021/9549287

    Article  PubMed  PubMed Central  Google Scholar 

  29. Zhang, Y., & Li, Y. (2020). Long non-coding RNA NORAD contributes to the proliferation, invasion and EMT progression of prostate cancer via the miR-30a-5p/RAB11A/WNT/beta-catenin pathway. Cancer Cell International, 20, 571. https://doi.org/10.1186/s12935-020-01665-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Savagner, P. (2010). The epithelial-mesenchymal transition (EMT) phenomenon. Annals of Oncology, 21(7), vii89-92.

    Article  PubMed  Google Scholar 

  31. Chen, T., You, Y., Jiang, H., & Wang, Z. Z. (2017). Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. Journal of Cellular Physiology, 232, 3261–3272. https://doi.org/10.1002/jcp.25797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang, L., Zhao, S., & Yu, M. (2019). Mechanism of low expression of miR-30a-5p on epithelial-mesenchymal transition and metastasis in ovarian cancer. DNA and Cell Biology, 38, 341–351. https://doi.org/10.1089/dna.2018.4396

    Article  CAS  PubMed  Google Scholar 

  33. Chen, S., et al. (2021). miR-30a-5p regulates viability, migration, and invasion of lung adenocarcinoma cells via targeting ECT2. Computational and Mathematical Methods in Medicine, 2021, 6241469. https://doi.org/10.1155/2021/6241469

    Article  PubMed  PubMed Central  Google Scholar 

  34. Zhang, Z., et al. (2020). The miR-30a-5p/CLCF1 axis regulates sorafenib resistance and aerobic glycolysis in hepatocellular carcinoma. Cell Death & Disease, 11, 902. https://doi.org/10.1038/s41419-020-03123-3

    Article  CAS  Google Scholar 

  35. Tao, K., et al. (2021). Vascular endothelial cell-derived exosomal miR-30a-5p inhibits lung adenocarcinoma malignant progression by targeting CCNE2. Carcinogenesis, 42, 1056–1067. https://doi.org/10.1093/carcin/bgab051

    Article  CAS  PubMed  Google Scholar 

  36. Li, W., Han, F., Fu, M., & Wang, Z. (2020). High expression of VCAN is an independent predictor of poor prognosis in gastric cancer. Journal of International Medical Research, 48, 300060519891271. https://doi.org/10.1177/0300060519891271

    Article  CAS  PubMed  Google Scholar 

  37. Cheng, Y., et al. (2020). VUp-regulation of VCAN promotes the proliferation, invasion and migration and serves as a biomarker in gastric cancer. Oncotargets and Therapy, 13, 8665–8675. https://doi.org/10.2147/OTT.S262613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mitsui, Y., et al. (2017). Versican promotes tumor progression, metastasis and predicts poor prognosis in renal carcinoma. Molecular Cancer Research, 15, 884–895. https://doi.org/10.1158/1541-7786.MCR-16-0444

    Article  CAS  PubMed  Google Scholar 

  39. Li, R., Hou, S., Zou, M., Ye, K., & Xiang, L. (2021). miR-543 impairs cell proliferation, migration, and invasion in breast cancer by suppressing VCAN. Biochemical and Biophysical Research Communications, 570, 191–198. https://doi.org/10.1016/j.bbrc.2021.07.005

    Article  CAS  PubMed  Google Scholar 

  40. Zhao, X., et al. (2017). MiR-135a-5p modulates biological functions of thyroid carcinoma cells via targeting VCAN 3’-UTR. Cancer Biomarkers, 20, 207–216. https://doi.org/10.3233/CBM-170566

    Article  CAS  PubMed  Google Scholar 

  41. Xiang, J., Bian, C., Wang, H., Huang, S., & Wu, D. (2015). MiR-203 down-regulates Rap1A and suppresses cell proliferation, adhesion and invasion in prostate cancer. Journal of Experimental & Clinical Cancer Research, 34, 8. https://doi.org/10.1186/s13046-015-0125-x

    Article  CAS  Google Scholar 

  42. Minn, A. J., et al. (2005). Genes that mediate breast cancer metastasis to lung. Nature, 436, 518–524. https://doi.org/10.1038/nature03799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Reina, M. & Espel, E (2017) Role of LFA-1 and ICAM-1 in cancer. Cancers (Basel), 9, 153. https://doi.org/10.3390/cancers9110153.

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Funding

This study was supported in part by grants from Health Science and Technology Project of Zhejiang Province – General Project(2021KY1152).

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Authors and Affiliations

  1. Department of Respiratory Medicine, Yuecheng District, Shaoxing People’s Hospital (Shaoxing Hospital), Zhejiang University School of Medicine, 568 Zhongxing North Road, Shaoxing City, 312000, Zhejiang Province, China

    E. Qin, Shuojia Gu, Yimin Guo & Guimei Pu

  2. Department of Integrated Traditional Chinese and Western Medicine & Geriatrics, Shaoxing People’s Hospital (Shaoxing Hospital), Zhejiang University School of Medicine, Shaoxing City, 312000, Zhejiang Province, China

    Liyan Wang

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Contributions

E.Q. participated in the design and interpretation of the data and drafting/revising the manuscript. G.M.P and S.J.G conceived of the study, and participated in its design and interpretation and helped to draft the manuscript. Y.M.G performed the statistical analysis and revised the manuscript critically. L.Y.W participated in its design and interpretation and helped to revise the manuscript critically.

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Correspondence to Guimei Pu.

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Qin, E., Gu, S., Guo, Y. et al. MiRNA-30a-5p/VCAN Arrests Tumor Metastasis via Modulating the Adhesion of Lung Adenocarcinoma Cells. Appl Biochem Biotechnol 195, 7568–7582 (2023). https://doi.org/10.1007/s12010-023-04444-7

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