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Circular RNA hsa_circ_0002052 promotes osteosarcoma via modulating miR-382/STX6 axis

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Abstract

Circular RNAs (circRNAs) exert pivotal effects on regulating the progression of osteosarcoma (OS). It was found through microarray analysis that circ-0002052 is abnormally expressed in OS, but the role of circ-0002052 in OS remains obscure. The results of this research manifested that relative to that in non-tumor controls, circ-0002052 level was raised in OS tissues. Up-regulated circ-0002052 was associated with advanced stage, tumor size, and metastasis. Additionally, circ-0002052 elevation indicated a low survival rate in OS patients and silencing of circ-0002052 suppressed proliferation, migration, and invasion of OS cells. It was proved that circ-0002052 sponged miR-382 and stimulated STX6 expression, thus activating Wnt/β-catenin. The function of circ-0002052 reduction in OS cells was effectively reversed by miR-382 suppression. To sum up, it can be concluded that circ-0002052, functioning as a sponge for miR-382, enhances the activation of Wnt/β-catenin mediated by STX6 to stimulate the progression of OS, and circ-0002052 may be an underlying treatment target and a biomarker for prognosis of osteosarcoma.

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Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

References

  1. Lee YJ, Chung JG, Chien YT, Lin SS, Hsu FT. Suppression of ERK/NF-kappaB activation is associated with amentoflavone-inhibited osteosarcoma progression in vivo. Anticancer Res. 2019;39(7):3669–755. https://doi.org/10.21873/anticanres.13515.

    Article  PubMed  Google Scholar 

  2. Zhou J, Xiao X, Wang W, Luo Y. Association between PTEN and clinical-pathological features of osteosarcoma. Biosci Rep. 2019;39(7):BSR20190954. https://doi.org/10.1042/BSR20190954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Yu WC, Chen HH, Qu YY, Xu CW, Yang C, Liu Y. MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A. Biosci Rep. 2019;39(7):BSR20190198. https://doi.org/10.1042/BSR20190198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mu Y, Zhang L, Chen X, Chen S, Shi Y, Li J. Silencing microRNA-27a inhibits proliferation and invasion of human osteosarcoma cells through the SFRP1-dependent Wnt/beta-catenin signaling pathway. Biosci Rep. 2019;39(6):BSR20182366. https://doi.org/10.1042/BSR20182366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Dou Y, Zhu K, Sun Z, Geng X, Fang Q. Screening of disorders associated with osteosarcoma by integrated network analysis. Biosci Rep. 2019;39(5):BSR20190235. https://doi.org/10.1042/BSR20190235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xi Y, Fowdur M, Liu Y, Wu H, He M, Zhao J. Differential expression and bioinformatics analysis of circRNA in osteosarcoma. Biosci Rep. 2019;39(5):BSR20181514. https://doi.org/10.1042/BSR20181514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bian L, Zhi X, Ma L, Zhang J, Chen P, Sun S, Li J, Sun Y, Qin J. Hsa_circRNA_103809 regulated the cell proliferation and migration in colorectal cancer via miR-532-3p/FOXO4 axis. Biochem Biophys Res Commun. 2018;505(2):346–52. https://doi.org/10.1016/j.bbrc.2018.09.073.

    Article  CAS  PubMed  Google Scholar 

  8. Luan W, Shi Y, Zhou Z, Xia Y, Wang J. CircRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis. Biochem Biophys Res Commun. 2018;502(1):22–9. https://doi.org/10.1016/j.bbrc.2018.05.114.

    Article  CAS  PubMed  Google Scholar 

  9. Zhan W, Liao X, Chen Z, Li L, Tian T, Yu L, Wang W, Hu Q. Circular RNA hsa_circRNA_103809 promoted hepatocellular carcinoma development by regulating miR-377-3p/FGFR1/ERK axis. J Cell Physiol. 2019. https://doi.org/10.1002/jcp.29092.

    Article  PubMed  Google Scholar 

  10. Yu J, Yang M, Zhou B, Luo J, Zhang Z, Zhang W, Yan Z. CircRNA-104718 acts as competing endogenous RNA and promotes hepatocellular carcinoma progression through microRNA-218-5p/TXNDC5 signaling pathway. Clin Sci. 2019;133(13):1487–503. https://doi.org/10.1042/CS20190394.

    Article  CAS  PubMed  Google Scholar 

  11. Zhao F, Han Y, Liu Z, Zhao Z, Li Z, Jia K. circFADS2 regulates lung cancer cells proliferation and invasion via acting as a sponge of miR-498. Biosci Rep. 2018;38(4):BSR20180570. https://doi.org/10.1042/BSR20180570.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ma HB, Yao YN, Yu JJ, Chen XX, Li HF. Extensive profiling of circular RNAs and the potential regulatory role of circRNA-000284 in cell proliferation and invasion of cervical cancer via sponging miR-506. Am J Transl Res. 2018;10(2):592–604.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Li XN, Wang ZJ, Ye CX, Zhao BC, Li ZL, Yang Y. RNA sequencing reveals the expression profiles of circRNA and indicates that circDDX17 acts as a tumor suppressor in colorectal cancer. J Exp Clin Cancer Res. 2018;37(1):325. https://doi.org/10.1186/s13046-018-1006-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Li B, Xie F, Zheng FX, Jiang GS, Zeng FQ, Xiao XY. Overexpression of CircRNA BCRC4 regulates cell apoptosis and MicroRNA-101/EZH2 signaling in bladder cancer. J Huazhong Univ Sci Technol Med Sci. 2017;37(6):886–90. https://doi.org/10.1007/s11596-017-1822-9.

    Article  CAS  PubMed  Google Scholar 

  15. Xiao-Long M, Kun-Peng Z, Chun-Lin Z. Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma. J Cancer. 2018;9(10):1856–62. https://doi.org/10.7150/jca.24619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang L, Chen M, Pan J, Yu W. Circular RNA circNASP modulates the malignant behaviors in osteosarcoma via miR-1253/FOXF1 pathway. Biochem Biophys Res Commun. 2018;500(2):511–7. https://doi.org/10.1016/j.bbrc.2018.04.131.

    Article  CAS  PubMed  Google Scholar 

  17. Jiang X, Wu X, Chen F, He W, Chen X, Liu L, Tang H. The profiles and networks of miRNA, lncRNA, mRNA, and circRNA in benzo(a)pyrene-transformed bronchial epithelial cells. J Toxicol Sci. 2018;43(4):281–9. https://doi.org/10.2131/jts.43.281.

    Article  CAS  PubMed  Google Scholar 

  18. Li Q, Wang H, Peng H, Huang Q, Huyan T, Huang Q, Yang H, Shi J. MicroRNAs: key players in bladder cancer. Mol Diagn Ther. 2019. https://doi.org/10.1007/s40291-019-00410-4.

    Article  PubMed  Google Scholar 

  19. Pishkari S, Paryan M, Hashemi M, Baldini E, Mohammadi-Yeganeh S. The role of microRNAs in different types of thyroid carcinoma: a comprehensive analysis to find new miRNA supplementary therapies. J Endocrinol Invest. 2018;41(3):269–83. https://doi.org/10.1007/s40618-017-0735-6.

    Article  CAS  PubMed  Google Scholar 

  20. Wang M, Xie R, Si H, Shen B. Integrated bioinformatics analysis of miRNA expression in osteosarcoma. Artif Cells Nanomed Biotechnol. 2017;45(5):936–43. https://doi.org/10.1080/21691401.2016.1196456.

    Article  CAS  PubMed  Google Scholar 

  21. Xu M, Jin H, Xu CX, Sun B, Song ZG, Bi WZ, Wang Y. miR-382 inhibits osteosarcoma metastasis and relapse by targeting Y box-binding protein 1. Mol Ther. 2015;23(1):89–988. https://doi.org/10.1038/mt.2014.197.

    Article  CAS  PubMed  Google Scholar 

  22. Xia P, Gao X, Shao L, Chen Q, Li F, Wu C, Zhang W, Sun Y. Down-regulation of RAC2 by small interfering RNA restrains the progression of osteosarcoma by suppressing the Wnt signaling pathway. Int J Biol Macromol. 2019;137:1221–31. https://doi.org/10.1016/j.ijbiomac.2019.07.016.

    Article  CAS  PubMed  Google Scholar 

  23. Tan T, Chen J, Hu Y, Wang N, Chen Y, Yu T, Lin D, Yang S, Luo J, Luo X. Dihydrotanshinone I inhibits the growth of osteosarcoma through the Wnt/beta-catenin signaling pathway. Onco Targets Ther. 2019;12:5111–222. https://doi.org/10.2147/OTT.S204574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang Q, Shi SY, Ji HB, Xing SX. LncRNA BE503655 inhibits osteosarcoma cell proliferation, invasion/migration via Wnt/beta-catenin pathway. Biosci Rep. 2019;39(7):BSR20182200. https://doi.org/10.1042/BSR20182200.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jin X, Feng CY, Xiang Z, Chen YP, Li YM. CircRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of nonalcoholic steatohepatitis. Oncotarget. 2016;7(41):66455–67. https://doi.org/10.18632/oncotarget.12186.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Su Y, Xu C, Liu Y, Hu Y, Wu H. Circular RNA hsa_circ_0001649 inhibits hepatocellular carcinoma progression via multiple miRNAs sponge. Aging. 2019. https://doi.org/10.18632/aging.101988.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rong D, Sun H, Li Z, Liu S, Dong C, Fu K, Tang W, Cao H. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget. 2017;8(42):73271–81. https://doi.org/10.18632/oncotarget.19154.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhou B, Yu JW. A novel identified circular RNA, circRNA_010567, promotes myocardial fibrosis via suppressing miR-141 by targeting TGF-beta1. Biochem Biophys Res Commun. 2017;487(4):769–75. https://doi.org/10.1016/j.bbrc.2017.04.044.

    Article  CAS  PubMed  Google Scholar 

  29. Feng J, Qi B, Guo L, Chen LY, Wei XF, Liu YZ, Zhao BS. miR-382 functions as a tumor suppressor against esophageal squamous cell carcinoma. World J Gastroenterol. 2017;23(23):4243–51. https://doi.org/10.3748/wjg.v23.i23.4243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yao H, Xia D, Li ZL, Ren L, Wang MM, Chen WS, Hu ZC, Yi GP, Xu L. MiR-382 functions as tumor suppressor and chemosensitizer in colorectal cancer. Biosci Rep. 2018. https://doi.org/10.1042/BSR20180441.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Xu M, Jin H, Xu CX, Sun B, Mao Z, Bi WZ, Wang Y. miR-382 inhibits tumor growth and enhance chemosensitivity in osteosarcoma. Oncotarget. 2014;5(19):9472–83. https://doi.org/10.18632/oncotarget.2418.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors

Contributions

PZ made substantial contributions to conception and design. JR, RS, and YL made acquisition of data. PZ and JR performed the experiments. JW and RS wrote the draft manuscript. All authors contributed to the reviewing of the manuscript, and approved the final manuscript for submission.

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Correspondence to Rong Sun.

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The authors have declared no conflict of interest.

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The study was performed in accordance with the Declaration of Helsinki and obtained the approval from the Ethics Committee of the First People’s Hospital of Qujing.

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Zhang, Pr., Ren, J., Wan, Js. et al. Circular RNA hsa_circ_0002052 promotes osteosarcoma via modulating miR-382/STX6 axis. Human Cell 33, 810–818 (2020). https://doi.org/10.1007/s13577-020-00335-9

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  • DOI: https://doi.org/10.1007/s13577-020-00335-9

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