Abstract
To explore the expression and the functions of SRPK1 in osteosarcoma, we retrieved transcription profiling dataset by array of human bone specimens from patients with osteosarcoma from ArrayExpress (accession E-MEXP-3628) and from Gene Expression Omnibus (accession GSE16102) and analyzed expression level of SRPK1 and prognostic value in human osteosarcoma. Then we examined the effect of differential SRPK1 expression levels on the progression of osteosarcoma, including cell proliferation, cell cycle, apoptosis, and investigated its underlying molecular mechanism using in vitro osteosarcoma cell lines and in vivo nude mouse xenograft models. High expression level of SRPK1 was found in human osteosarcoma tissues and cell lines as compared to the normal bone tissues and osteoblast cells, and predicted poor prognosis of human osteosarcoma. Overexpression of SRPK1 in osteosarcoma U2OS cells led to cell proliferation but inhibition of apoptosis. In contrast, knockdown of SRPK1 in HOS cells impeded cell viability and induction of apoptosis. Moreover, silencing SRPK1 inhibited osteosarcoma tumor growth in nude mice. Mechanistic studies revealed that SRPK1 promoted cell cycle transition in osteosarcoma cells and activation of NF-κB is required for SRPK1 expression and its pro-survival signaling. SRPK1 promoted human osteosarcoma cell proliferation and tumor growth by regulating NF-κB signaling pathway.
-
Author contributions: Yubao Gong designed the study. Yubao Gong, Chen Yang and Zhengren Wei, performed the experiments. Yubao Gong and Chen Yang contributed to the writing of the manuscript. Yubao Gong, Chen Yang and Jianguo Liu performed the analyses and calculations. All authors read and approved the final manuscript.
-
Research funding: None declared.
-
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
-
Conflict of interest statement Ethics approval: This study was approved by the Institutional Animal Care and Use Committee of the First Hospital of Jilin University.
-
Conflict of interest statement Availability of data and materials: Please contact the corresponding author (Yubao Gong) for data requests.
References
Amin, E.M., Oltean, S., Hua, J., Gammons, M.V., Hamdollah-Zadeh, M., Welsh, G.I., Cheung, M.K., Ni, L., Kase, S., Rennel, E.S., et al.. (2011). WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell 20: 768–780, https://doi.org/10.1016/j.ccr.2011.10.016.Suche in Google Scholar PubMed PubMed Central
Bielack, S.S., Kempf-Bielack, B., Delling, G., Exner, G.U., Flege, S., Helmke, K., Kotz, R., Salzer-Kuntschik, M., Werner, M., Winkelmann, W., et al.. (2002). Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J. Clin. Oncol. 20: 776–790, https://doi.org/10.1200/jco.2002.20.3.776.Suche in Google Scholar
Bielli, P., Bordi, M., Di Biasio, V., and Sette, C. (2014). Regulation of BCL-X splicing reveals a role for the polypyrimidine tract binding protein (PTBP1/hnRNP I) in alternative 5′ splice site selection. Nucl. Acids Res. 42: 12070–12081, https://doi.org/10.1093/nar/gku922.Suche in Google Scholar PubMed PubMed Central
Catz, S.D. and Johnson, J.L. (2001). Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20: 7342–7351, https://doi.org/10.1038/sj.onc.1204926.Suche in Google Scholar PubMed
Chang, Y., Wu, Q., Tian, T., Li, L., Guo, X., Feng, Z., Zhou, J., Zhang, L., Zhou, S., Feng, G., et al.. (2015). The influence of SRPK1 on glioma apoptosis, metastasis, and angiogenesis through the PI3K/Akt signaling pathway under normoxia. Tumour Biol. 36: 6083–6093, https://doi.org/10.1007/s13277-015-3289-2.Suche in Google Scholar PubMed
Cheng, S., Hsia, C.Y., Leone, G., and Liou, H.C. (2003). Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel−/− B cells. Oncogene 22: 8472–8486, https://doi.org/10.1038/sj.onc.1206917.Suche in Google Scholar PubMed
Cramer, M., Nagy, I., Murphy, B.J., Gassmann, M., Hottiger, M.O., Georgiev, O., and Schaffner, W. (2005). NF-kappaB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells. Biol. Chem. 386: 865–872, https://doi.org/10.1515/bc.2005.101.Suche in Google Scholar PubMed
Duyao, M.P., Buckler, A.J., and Sonenshein, G.E. (1990). Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter. Proc. Natl. Acad. Sci. U.S.A. 87: 4727–4731, https://doi.org/10.1073/pnas.87.12.4727.Suche in Google Scholar PubMed PubMed Central
Guttridge, D.C., Albanese, C., Reuther, J.Y., Pestell, R.G., and Baldwin, A.S.Jr. (1999). NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell Biol. 19: 5785–5799, https://doi.org/10.1128/mcb.19.8.5785.Suche in Google Scholar PubMed PubMed Central
Han, X., Yang, J., Jia, Z., Wei, P., Zhang, H., Lv, W., Sun, J., and Huo, Q. (2017). Knockdown of serine-arginine protein kinase 1 inhibits the growth and migration in renal cell carcinoma cells. Oncol. Res. 25: 389–395, https://doi.org/10.3727/096504016x14743324568129.Suche in Google Scholar
Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144: 646–674, https://doi.org/10.1016/j.cell.2011.02.013.Suche in Google Scholar PubMed
Hayden, M.S. and Ghosh, S. (2008). Shared principles in NF-kappaB signaling. Cell 132: 344–362, https://doi.org/10.1016/j.cell.2008.01.020.Suche in Google Scholar PubMed
Huang, T.T., Kudo, N., Yoshida, M., and Miyamoto, S. (2000). A nuclear export signal in the N-terminal regulatory domain of IkappaB alpha controls cytoplasmic localization of inactive NF-kappaB/IkappaB alpha complexes. Proc. Natl. Acad. Sci. U.S.A. 97: 1014–1019, https://doi.org/10.1073/pnas.97.3.1014.Suche in Google Scholar PubMed PubMed Central
Janeway, K.A., Barkauskas, D.A., Krailo, M.D., Meyers, P.A., Schwartz, C.L., Ebb, D.H., Seibel, N.L., Grier, H.E., Gorlick, R., and Marina, N. (2012). Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children’s Oncology Group. Cancer 118: 4597–4605, https://doi.org/10.1002/cncr.27414.Suche in Google Scholar PubMed PubMed Central
Karin, M. (2006). Nuclear factor-kappaB in cancer development and progression. Nature 441: 431–436, https://doi.org/10.1038/nature04870.Suche in Google Scholar PubMed
Karin, M., Cao, Y., Greten, F.R., and Li, Z.W. (2002). NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer 2: 301–310, https://doi.org/10.1038/nrc780.Suche in Google Scholar PubMed
Lee, J.H., Jo, Y.S., Kim, M.S., Yoo, N.J., and Lee, S.H. (2017). Inactivating frameshift mutation of putative tumor suppressor genes PLA2R1 and SRPK1 in gastric and colorectal cancers. Cancer Genet 210: 34–35, https://doi.org/10.1016/j.cancergen.2016.11.005.Suche in Google Scholar PubMed
Li, Z.W., Chen, H., Campbell, R.A., Bonavida, B., and Berenson, J.R. (2008). NF-kappaB in the pathogenesis and treatment of multiple myeloma. Curr. Opin. Hematol. 15: 391–399, https://doi.org/10.1097/moh.0b013e328302c7f4.Suche in Google Scholar
Liu, H., Hu, X., Zhu, Y., Jiang, G., and Chen, S. (2016). Up-regulation of SRPK1 in non-small cell lung cancer promotes the growth and migration of cancer cells. Tumour Biol. 37: 7287–7293, https://doi.org/10.1007/s13277-015-4510-z.Suche in Google Scholar PubMed
Long, J.C. and Caceres, J.F. (2009). The SR protein family of splicing factors: master regulators of gene expression. Biochem. J. 417: 15–27, https://doi.org/10.1042/bj20081501.Suche in Google Scholar PubMed
Longhi, A., Errani, C., Gonzales-Arabio, D., Ferrari, C., and Mercuri, M. (2008). Osteosarcoma in patients older than 65 years. J. Clin. Oncol. 26: 5368–5373, https://doi.org/10.1200/jco.2007.14.9104.Suche in Google Scholar PubMed
Mavrou, A. and Oltean, S. (2016). SRPK1 inhibition in prostate cancer: a novel anti-angiogenic treatment through modulation of VEGF alternative splicing. Pharmacol. Res. 107: 276–281, https://doi.org/10.1016/j.phrs.2016.03.013.Suche in Google Scholar PubMed PubMed Central
McKenna, R.J., Schwinn, C.P., Soong, K.Y., and Higinbotham, N.L. (1966). Sarcomata of the osteogenic series (osteosarcoma, fibrosarcoma, chondrosarcoma, parosteal osteogenic sarcoma, and sarcomata arising in abnormal bone): an analysis of 552 cases. J. Bone Joint Surg. Am. 48: 1–26, https://doi.org/10.2106/00004623-196648010-00001.Suche in Google Scholar
Mirabello, L., Troisi, R.J., and Savage, S.A. (2009). Osteosarcoma incidence and survival rates from 1973 to 2004: data from the surveillance, epidemiology, and end results program. Cancer 115: 1531–1543, https://doi.org/10.1002/cncr.24121.Suche in Google Scholar PubMed PubMed Central
Moon, D.O., Kim, M.O., Kang, S.H., Choi, Y.H., and Kim, G.Y. (2009). Sulforaphane suppresses TNF-α-mediated activation of NF-kappaB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3. Cancer Lett. 274: 132–142, https://doi.org/10.1016/j.canlet.2008.09.013.Suche in Google Scholar PubMed
Olshavsky, N.A., Comstock, C.E., Schiewer, M.J., Augello, M.A., Hyslop, T., Sette, C., Zhang, J., Parysek, L.M., and Knudsen, K.E. (2010). Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene. Cancer Res. 70: 3975–3984, https://doi.org/10.1158/0008-5472.can-09-3468.Suche in Google Scholar
Ottaviani, G. and Jaffe, N. (2009). The epidemiology of osteosarcoma. Cancer Treat Res. 152: 3–13, https://doi.org/10.1007/978-1-4419-0284-9_1.Suche in Google Scholar PubMed
Papoutsopoulou, S., Nikolakaki, E., Chalepakis, G., Kruft, V., Chevaillier, P., and Giannakouros, T. (1999). SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Nucl. Acids Res. 27: 2972–2980, https://doi.org/10.1093/nar/27.14.2972.Suche in Google Scholar PubMed PubMed Central
Patel, M., Sachidanandan, M., and Adnan, M. (2019). Serine arginine protein kinase 1 (SRPK1): a moonlighting protein with theranostic ability in cancer prevention. Mol. Biol. Rep. 46: 1487–1497, https://doi.org/10.1007/s11033-018-4545-5.Suche in Google Scholar PubMed
Peng, Y., Lv, S., Li, Y., Zhu, J., Chen, S., Zhen, G., Cao, X., Wu, S., and Crane, J.L. (2020). Glucocorticoids disrupt skeletal angiogenesis through transrepression of NF-kappaB-Mediated preosteoclast pdgfb transcription in young mice. J. Bone Miner. Res. 35: 1188–1202, https://doi.org/10.1002/jbmr.3987.Suche in Google Scholar PubMed PubMed Central
Sen, R. and Baltimore, D. (1986). Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 47: 921–928, https://doi.org/10.1016/0092-8674(86)90807-x.Suche in Google Scholar
Sissons, H.A. (1976). The WHO classification of bone tumors. Recent Results Cancer Res. 54: 104–108, doi:https://doi.org/10.1007/978-3-642-80997-2_8.Suche in Google Scholar
Stacey, D.W. (2003). Cyclin D1 serves as a cell cycle regulatory switch in actively proliferating cells. Curr. Opin. Cell Biol. 15: 158–163, https://doi.org/10.1016/s0955-0674(03)00008-5.Suche in Google Scholar
Stiller, C.A., Bielack, S.S., Jundt, G., and Steliarova-Foucher, E. (2006). Bone tumours in European children and adolescents, 1978–1997. Report from the automated childhood cancer information system project. Eur. J. Cancer 42: 2124–2135, https://doi.org/10.1016/j.ejca.2006.05.015.Suche in Google Scholar PubMed
Tsai, P.W., Shiah, S.G., Lin, M.T., Wu, C.W., and Kuo, M.L. (2003). Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-κB signaling pathway. J. Biol. Chem. 278: 5750–5759, https://doi.org/10.1074/jbc.m204863200.Suche in Google Scholar PubMed
Tsuruta, F., Masuyama, N., and Gotoh, Y. (2002). The phosphatidylinositol 3-kinase (PI3K)-Akt pathway suppresses Bax translocation to mitochondria. J. Biol. Chem. 277: 14040–14047, https://doi.org/10.1074/jbc.m108975200.Suche in Google Scholar
Tzelepis, K., De Braekeleer, E., Aspris, D., Barbieri, I., Vijayabaskar, M.S., Liu, W.H., Gozdecka, M., Metzakopian, E., Toop, H.D., Dudek, M., et al.. (2018). SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4. Nat. Commun. 9: 5378, https://doi.org/10.1038/s41467-018-07620-0.Suche in Google Scholar PubMed PubMed Central
van Roosmalen, W., Le Devedec, S.E., Golani, O., Smid, M., Pulyakhina, I., Timmermans, A.M., Look, M.P., Zi, D., Pont, C., de Graauw, M., et al.. (2015). Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant. J. Clin. Invest. 125: 1648–1664, https://doi.org/10.1172/jci74440.Suche in Google Scholar
Wang, P., Zhou, Z., Hu, A., Ponte de Albuquerque, C., Zhou, Y., Hong, L., Sierecki, E., Ajiro, M., Kruhlak, M., Harris, C., et al.. (2014). Both decreased and increased SRPK1 levels promote cancer by interfering with PHLPP-mediated dephosphorylation of Akt. Mol. Cell. 54: 378–391, https://doi.org/10.1016/j.molcel.2014.03.007.Suche in Google Scholar PubMed PubMed Central
Wang, F., Zhou, J., Xie, X., Hu, J., Chen, L., Hu, Q., Guo, H., and Yu, C. (2015). Involvement of SRPK1 in cisplatin resistance related to long non-coding RNA UCA1 in human ovarian cancer cells. Neoplasma 62: 432–438, https://doi.org/10.4149/neo_2015_051.Suche in Google Scholar PubMed
Wang, H., Ge, W., Jiang, W., Li, D., and Ju, X. (2018). SRPK1siRNA suppresses K562 cell growth and induces apoptosis via the PARPcaspase3 pathway. Mol. Med. Rep. 17: 2070–2076, https://doi.org/10.3892/mmr.2017.8032.Suche in Google Scholar PubMed
Warren, C.F.A., Wong-Brown, M.W., and Bowden, N.A. (2019). BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 10: 177, https://doi.org/10.1038/s41419-019-1407-6.Suche in Google Scholar PubMed PubMed Central
Xu, Q., Liu, X., Liu, Z., Zhou, Z., Wang, Y., Tu, J., Li, L., Bao, H., Yang, L., and Tu, K. (2017). MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway. Mol. Cancer 16: 103, https://doi.org/10.1186/s12943-017-0675-y.Suche in Google Scholar PubMed PubMed Central
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2020-0394).
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Chemerin – exploring a versatile adipokine
- Research Articles/Short Communications
- Protein Structure and Function
- Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
- Cell Biology and Signaling
- SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
- LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
- Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
- CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction
Artikel in diesem Heft
- Frontmatter
- Review
- Chemerin – exploring a versatile adipokine
- Research Articles/Short Communications
- Protein Structure and Function
- Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study
- Cell Biology and Signaling
- SRPK1 promotes cell proliferation and tumor growth of osteosarcoma through activation of the NF-κB signaling pathway
- LINC00520 up-regulates SOX5 to promote cell proliferation and invasion by miR-4516 in human hepatocellular carcinoma
- Long non-coding RNA FAM66C regulates glioma growth via the miRNA/LATS1 signaling pathway
- CERKL alleviates ischemia reperfusion-induced nervous system injury through modulating the SIRT1/PINK1/Parkin pathway and mitophagy induction