https://doi.org/10.4081/ejh.2023.3631
Deletion of osteopontin in non-small cell lung cancer cells affects bone metabolism by regulating miR-34c/Notch1 axis: a clue to bone metastasis
Submitted: 8 December 2022
Accepted: 13 June 2023
Published: 26 July 2023
Accepted: 13 June 2023
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-49.
DOI: https://doi.org/10.3322/caac.21660
Friedlaender A, Addeo A, Russo A, Gregorc V, Cortinovis D, Rolfo CD. Targeted therapies in early stage NSCLC: hype or hope? Int J Mol Sci 2020;21:6329.
DOI: https://doi.org/10.3390/ijms21176329
Huang X, Shi X, Huang D, Li B, Lin N, Pan W, et al. Mutational characteristics of bone metastasis of lung cancer. Ann Palliat Med 2021;10:8818-26.
DOI: https://doi.org/10.21037/apm-21-1595
Popper HH. Progression and metastasis of lung cancer. Cancer Metastasis Rev 2016;35:75-91.
DOI: https://doi.org/10.1007/s10555-016-9618-0
Takahara Y, Nakase K, Nojiri M, Kato R, Shinomiya S, Oikawa T, et al. Relationship between clinical features and gene mutations in non-small cell lung cancer with osteoblastic bone metastasis. Cancer Treat Res Commun 2021;28:100440.
DOI: https://doi.org/10.1016/j.ctarc.2021.100440
Lamort AS, Giopanou I, Psallidas I, Stathopoulos GT. Osteopontin as a link between inflammation and cancer: the thorax in the spotlight. Cells 2019;8:815.
DOI: https://doi.org/10.3390/cells8080815
Berge G, Pettersen S, Grotterød I, Bettum IJ, Boye K, Mælandsmo GM. Osteopontin--an important downstream effector of S100A4-mediated invasion and metastasis. Int J Cancer 2011;129:780-90.
DOI: https://doi.org/10.1002/ijc.25735
Bruha R, Vitek L, Smid V. Osteopontin - A potential biomarker of advanced liver disease. Ann Hepatol 2020;19:344-52.
DOI: https://doi.org/10.1016/j.aohep.2020.01.001
Shi L, Hou J, Wang L, Fu H, Zhang Y, Song Y, et al. Regulatory roles of osteopontin in human lung cancer cell epithelial-to-mesenchymal transitions and responses. Clin Transl Med 2021;11:e486.
DOI: https://doi.org/10.1002/ctm2.486
Xu K, Tian X, Oh SY, Movassaghi M, Naber SP, Kuperwasser C, et al. The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis. Breast Cancer Res 2016;18:14.
DOI: https://doi.org/10.1186/s13058-016-0674-8
Qin X, Yan M, Wang X, Xu Q, Wang X, Zhu X, et al. Cancer-associated fibroblast-derived IL-6 promotes head and neck cancer progression via the osteopontin-NF-kappa B signaling pathway. Theranostics 2018;8:921-40.
DOI: https://doi.org/10.7150/thno.22182
Rodrigues LR, Teixeira JA, Schmitt FL, Paulsson M, Lindmark-Mänsson H. The role of osteopontin in tumor progression and metastasis in breast cancer. Cancer Epidemiol Biomarkers Prev 2007;16:1087-97.
DOI: https://doi.org/10.1158/1055-9965.EPI-06-1008
Zhang N, Li F, Gao J, Zhang S, Wang Q. Osteopontin accelerates the development and metastasis of bladder cancer via activating JAK1/STAT1 pathway. Genes Genomics 2020;42:467-75.
DOI: https://doi.org/10.1007/s13258-019-00907-6
Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol 2009;4:199-227.
DOI: https://doi.org/10.1146/annurev.pathol.4.110807.092222
Colden M, Dar AA, Saini S, Dahiya PV, Shahryari V, Yamamura S, et al. MicroRNA-466 inhibits tumor growth and bone metastasis in prostate cancer by direct regulation of osteogenic transcription factor RUNX2. Cell Death Dis 2017;8:e2572.
DOI: https://doi.org/10.1038/cddis.2017.15
Tang Z, Xu T, Li Y, Fei W, Yang G;Hong Y. Inhibition of CRY2 by STAT3/miRNA-7-5p promotes osteoblast differentiation through upregulation of CLOCK/BMAL1/P300 expression. Mol Ther Nucleic Acids 2020;19:865-76.
DOI: https://doi.org/10.1016/j.omtn.2019.12.020
Xu M, Jin H, Xu CX, Bi WZ;Wang Y. MiR-34c inhibits osteosarcoma metastasis and chemoresistance. Med Oncol 2014;31:972.
DOI: https://doi.org/10.1007/s12032-014-0972-x
Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, et al. miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet 2012;21:2991-3000.
DOI: https://doi.org/10.1093/hmg/dds129
Bae Y, Zeng HC, Chen YT, Ketkar S, Munivez E, Yu Z, et al. miRNA-34c suppresses osteosarcoma progression in vivo by targeting Notch and E2F. JBMR Plus 2022;6:e10623.
DOI: https://doi.org/10.1002/jbm4.10623
Zhang X. Interactions between cancer cells and bone microenvironment promote bone metastasis in prostate cancer. Cancer Commun (Lond) 2019;39:76.
DOI: https://doi.org/10.1186/s40880-019-0425-1
Li C, Qiu M, Chang L, Qi J, Zhang L, Ryffel B, et al. The osteoprotective role of USP26 in coordinating bone formation and resorption. Cell Death Differ 2022;29:1123-36.
DOI: https://doi.org/10.1038/s41418-021-00904-x
Liang X, Hou Y, Han L, Yu S, Zhang Y, Cao X, et al. ELMO1 regulates RANKL-stimulated differentiation and bone resorption of osteoclasts. Front Cell Dev Biol 2021;9:702916.
DOI: https://doi.org/10.3389/fcell.2021.702916
Bailey S, Karsenty G, Gundberg C, Vashishth D. Osteocalcin and osteopontin influence bone morphology and mechanical properties. Ann NY Acad Sci 2017;1409:79-84.
DOI: https://doi.org/10.1111/nyas.13470
Brook N, Brook E, Dharmarajan A, Dass CR;Chan A. Breast cancer bone metastases: pathogenesis and therapeutic targets. Int J Biochem Cell Biol 2018;96:63-78.
DOI: https://doi.org/10.1016/j.biocel.2018.01.003
Ishii T, Ohshima S, Ishida T, Mima T, Tabunoki Y, Kobayashi H, et al. Osteopontin as a positive regulator in the osteoclastogenesis of arthritis. Biochem Biophys Res Commun 2004;316:809-15.
DOI: https://doi.org/10.1016/j.bbrc.2004.02.124
Eriksen EF. Cellular mechanisms of bone remodeling. Rev Endocr Metab Disord 2010;11:219-27.
DOI: https://doi.org/10.1007/s11154-010-9153-1
Kim JM, Lin C, Stavre Z, Greenblatt MB, Shim JH. Osteoblast-osteoclast communication and bone homeostasis. Cells 2020;9:2073.
DOI: https://doi.org/10.3390/cells9092073
Hill M, Tran N. miRNA interplay: mechanisms and consequences in cancer. Dis Model Mech 2021;14:dmm047662.
DOI: https://doi.org/10.1242/dmm.047662
29. Liu S, Wang L, Zhang R. Corylin suppresses metastasis of breast cancer cells by modulating miR-34c/LINC00963 target. Libyan J Med 2021;16:1883224.
DOI: https://doi.org/10.1080/19932820.2021.1883224
Duan P, Chen S, Zeng Y, Xu H, Liu Y. Osteopontin upregulates Col IV expression by repressing miR-29a in human retinal capillary endothelial cells. Mol Ther Nucleic Acids 2020;20:242-51.
DOI: https://doi.org/10.1016/j.omtn.2020.02.001
Yu J, Canalis E. Notch and the regulation of osteoclast differentiation and function. Bone 2020;138:115474.
DOI: https://doi.org/10.1016/j.bone.2020.115474
Bai S, Kopan R, Zou W, Hilton MJ, Ong CT, Long F, et al. NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 2008;283:6509-18.
DOI: https://doi.org/10.1074/jbc.M707000200
Ethics Approval
This study was approved by the Ethics Committee on Human Research of the Ningbo First Hospital (approval number: 2022-201-5)How to Cite
Guo, J., Tong, C.-Y., Shi, J.-G., Li, X.-J., & Chen, X.-Q. (2023). Deletion of osteopontin in non-small cell lung cancer cells affects bone metabolism by regulating miR-34c/Notch1 axis: a clue to bone metastasis. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3631
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