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RHAMM regulates the growth and migration of lung adenocarcinoma A549 cell line by regulating Cdc2/CyclinB1 and MMP9 genes
Running title: RHAMM regulates the growth of lung adenocarcinoma cells

1 Department of Respiratory Medicine, Taizhou Municipal Hospital, Taizhou 318000, China
2 Department of Gastroenterology, Taizhou Municipal Hospital, Taizhou 318000, China
3 Department of Oncological Radiotherapy, The First People's Hospital of Hangzhou Fuyang, Hangzhou 311400, China
4 Department of Respiratory Medicine, Hangzhou Red Cross Hospital, Hangzhou 310003, China

Objective: The study aims to explore the effects of receptor of hyaluronan mediated motility (RHAMM) on the proliferation, invasion and migration of the lung adenocarcinoma (LUAD) cell line A549 and its targeted regulatory pathway.
Methods: Bioinformatics was used to analyze the differentially expressed genes in LUAD chips. The mRNA and protein expression level of Cdc2, CyclinB1, MMPs and epithelial-mesenchymal transition (EMT) related markers E-cadherin and Vimentin were tested by qRT-PCR and western blot in A549 cell line after silencing RHAMM. Cell proliferation, cell division cycle, migration and invasion abilities were tested in RHAMM knockdown A549 cells by flow cytometry and in vitro assays.
Results: Silencing RHAMM inhibited EMT, proliferation, migration and invasion of A549 cell line and induced cells to cluster at G2/M phase. In addition, after silencing RHAMM, the mRNA and protein expressions of Cdc2 and CyclinB1 were decreased while those of MMP9 were increased.
Conclusion: The findings suggest that RHAMM regulates cell division cycle by regulating Cdc2 and CyclinB1, and regulates extracellular matrix degradation by regulating MMP9. These targeted modulations regulate the occurrence and development of LUAD cells.
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1. R. L. Siegel, K. D. Miller, A. Jemal, Cancer statistics, 2016, CA Cancer J. Clin., 66 (2016), 7-30.

2. R. Wang, S. Zhang, X. Chen, N. Li, J. Li, R. Jia, et al., EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis, Mol. Cancer, 17 (2018), 166.

3. Y. An, K. L. Furber, S. Ji, Pseudogenes regulate parental gene expression via ceRNA network, J. Cell Mol. Med., 21 (2017), 185-192.

4. L. Peng, G. Chen, Z. Zhu, Z. Shen, C. Du, R. Zang, et al., Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung's disease, Oncotarget, 8 (2017), 808-818.

5. Y. Tay, J. Rinn, P. P. Pandolfi, The multilayered complexity of ceRNA crosstalk and competition, Nature, 505 (2014), 344-352.

6. S. Liu, P. Zhang, Z. Chen, M. Liu, X. Li, H. Tang, MicroRNA-7 downregulates XIAP expression to suppress cell growth and promote apoptosis in cervical cancer cells, FEBS Lett., 587 (2013), 2247-2253.

7. T. Bian, L. Zheng, D. Jiang, J. Liu, Overexpression of fibronectin type III domain containing 3B is correlated with epithelial-mesenchymal transition and predicts poor prognosis in lung adenocarcinoma, Exp. Ther. Med., 17 (2019), 3317-3326.

8. M. JD, Molecular pathogenesis of lung cancer, Lung Cancer, 29 (2000), 37-38.

9. N. Schatz-Siemers, Y. T. Chen, Z. Chen, D. Wang, L. H. Ellenson, Y. N. Du, Expression of the Receptor for Hyaluronic Acid-Mediated Motility (RHAMM) in Endometrial Cancer is Associated With Adverse Histologic Parameters and Tumor Progression, Appl. Immunohistochem. Mol. Morphol., 2019.

10. C. Tolg, S. R. Hamilton, K. A. Nakrieko, F. Kooshesh, P. Walton, J. B. McCarthy, et al., Rhamm-/- fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair, J. Cell Biol., 175 (2006), 1017-1028.

11. E. A. Turley, Purification of a hyaluronate-binding protein fraction that modifies cell social behavior, Biochem. Biophys. Res. Commun., 108 (1982), 1016-1024.

12. J. P. Lydon, F. J. DeMayo, C. R. Funk, S. K. Mani, A. R. Hughes, C. A. Montgomery, et al., Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities, Genes Dev., 9 (1995), 2266-2278.

13. S. Mohapatra, X. Yang, J. A. Wright, E. A. Turley, A. H. Greenberg, Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression, J. Exp. Med., 183 (1996), 1663-1668.

14. A. Hamai, H. Benlalam, F. Meslin, M. Hasmim, T. Carré, I. Akalay, et al., Immune surveillance of human cancer: if the cytotoxic T-lymphocytes play the music, does the tumoral system call the tune?, Tissue Antigens, 75 (2010), 1-8.

15. H. M. Muller, A. Widschwendter, H. Fieg, L. Ivarsson, G. Goebel, E. Perkmann, et al., DNA methylation in serum of breast cancer patients: an independent prognostic marker, Cancer Res., 63 (2003), 7641-7645.

16. D. Wang, N. Narula, S. Azzopardi, R. S. Smith, A. Nasar, N. K. Altorki, et al., Expression of the receptor for hyaluronic acid mediated motility (RHAMM) is associated with poor prognosis and metastasis in non-small cell lung carcinoma, Oncotarget, 7 (2016), 39957-39969.

17. F. Augustin, M. Fiegl, T. Schmid, G. Pomme, W. Sterlacci, A. Tzankov, Receptor for hyaluronic acid-mediated motility (RHAMM, CD168) expression is prognostically important in both nodal negative and nodal positive large cell lung cancer, J. Clin. Pathol., 68 (2015), 368-373.

18. A. Lugli, I. Zlobec, U. Gunthert, P. Minoo, K. Baker, L. Tornillo, et al., Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer, Mod. Pathol., 19 (2006), 1302-1309.

19. I. Zlobec, L. Terracciano, L. Tornillo, U. Günthert, T. Vuong, J. R. Jass, et al., Role of RHAMM within the hierarchy of well-established prognostic factors in colorectal cancer, Gut, 57 (2008), 1413-1419.

20. V. H. Koelzer, B. Huber, V. Mele, G. Iezzi, Expression of the hyaluronan-mediated motility receptor RHAMM in tumor budding cells identifies aggressive colorectal cancers, Hum. Pathol., 46 (2015), 1573-1581.

21. V. Mele, L. Sokol, V. H. Kolzer, D. Pfaff, M. G. Muraro, I. Keller, et al., The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer, Oncotarget, 8 (2017), 70617-70629.

22. S. T. Buttermore, M. S. Hoffman, A. Kumar, A. Champeaux, S. V. Nicosia, P. A. Kruk, Increased RHAMM expression relates to ovarian cancer progression, J. Ovarian. Res., 10 (2017), 66.

23. J. M. Song, J. Im, R. S. Nho, Y. H. Han, P. Upadhyaya, F. Kassie, Hyaluronan-CD44/RHAMM interaction-dependent cell proliferation and survival in lung cancer cells, Mol. Carcinog, 58 (2019), 321-333.

24. K. Kouvidi, A. Berdiaki, M. Tzardi, E. Karousou, A. Passi, D. Nikitovic, et al., Receptor for hyaluronic acid- mediated motility (RHAMM) regulates HT1080 fibrosarcoma cell proliferation via a beta-catenin/c-myc signaling axis, Biochim. Biophys. Acta., 1860 (2016), 814-824.

25. A. R. Jordan, S. D. Lokeshwar, L. E. Lopez, M. Hennig, J. Chipollini, T. Yates, et al., Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer, Oncotarget, 8 (2017), 24262-24274.

26. S. Matou-Nasri, J. Gaffney, S. Kumar, M. Slevin, Oligosaccharides of hyaluronan induce angiogenesis through distinct CD44 and RHAMM-mediated signalling pathways involving Cdc2 and gamma-adducin, Int. J. Oncol., 35 (2009), 761-773.

27. P. Pongcharoen, A. Jinawath, R. Tohtong, Silencing of CD44 by siRNA suppressed invasion, migration and adhesion to matrix, but not secretion of MMPs, of cholangiocarcinoma cells, Clin. Exp. Metastasis., 28 (2011), 827-839.

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