Skip to main content
Log in

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data type used to support the findings of this study are available from the corresponding author upon request.

References

  1. Dai X, Ma W, He X, Jha RK. Review of therapeutic strategies for osteosarcoma, chondrosarcoma, and Ewing’s sarcoma. Med Sci Monit. 2011;17(8):A177–90.

    Article  Google Scholar 

  2. Rasalkar DD, Chu WC, Lee V, Paunipagar BK, Cheng FW, Li CK. Pulmonary metastases in children with osteosarcoma: characteristics and impact on patient survival. Pediatr Radiol. 2010;41(2):227–36.

    Article  PubMed  Google Scholar 

  3. Wang SH, Zhang WJ, Wu XC, Weng MZ, Zhang MD, Cai Q, et al. The lncRNA MALAT1 functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-363-3p in gallbladder cancer. J Cell Mol Med. 2016;20(12):2299–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sas-Chen A, Aure MR, Leibovich L, Carvalho S, Enuka Y, Korner C, et al. LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer. Embo Mol Med. 2016;8(9):1052–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. Rna Biol. 2014;9(6):703–19.

    Article  Google Scholar 

  6. Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. 2007;13(3):313–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lv J, Ma L, Chen XL, Huang XH, Wang Q. Downregulation of LncRNAH19 and MiR-675 promotes migration and invasion of human hepatocellular carcinoma cells through AKT/GSK-3beta/Cdc25A signaling pathway. J Huazhong Univ Sci Technolog Med Sci. 2014;34(3):363–9.

    Article  CAS  PubMed  Google Scholar 

  8. Guo W, Jiang H, Li H, Li F, Yu Q, Liu Y, et al. LncRNA-SRA1 suppresses osteosarcoma cell proliferation while promoting cell apoptosis. Technol Cancer Res Treat. 2019;18:1078109086.

    Article  Google Scholar 

  9. Zhang F, Zhu Y, Fan G, Hu S. MicroRNA-2682-3p inhibits osteosarcoma cell proliferation by targeting CCND2, MMP8 and Myd88. Oncol Lett. 2018;16(3):3359–64.

    PubMed  PubMed Central  Google Scholar 

  10. Tang XF, Cao Y, Peng DB, Zhao GS, Zeng Y, Gao ZR, et al. Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients. Cancer Manag Res. 2019;11:547–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Qu J, Li M, Zhong W, Hu C. Competing endogenous RNA in cancer: a new pattern of gene expression regulation. Int J Clin Exp Med. 2015;8(10):17110–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Chen T, Li Y, Cao W, Liu Y. miR-491-5p inhibits osteosarcoma cell proliferation by targeting PKM2. Oncol Lett. 2018;16(5):6472–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Sweetnam R. Osteosarcoma. Br J Hosp Med. 1982;28(2):112–21.

    CAS  PubMed  Google Scholar 

  14. Liu K, Sun X, Zhang Y, Liu L, Yuan Q. MiR-598: a tumor suppressor with biomarker significance in osteosarcoma. Life Sci. 2017;188:141–8.

    Article  CAS  PubMed  Google Scholar 

  15. Fu D, Lu C, Qu X, Li P, Chen K, Shan L, et al. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis. Aging (Albany NY). 2019;11(19):8374–85.

    Article  CAS  PubMed  Google Scholar 

  16. Zheng S, Jiang F, Ge D, Tang J, Chen H, Yang J, et al. LncRNA SNHG3/miRNA-151a-3p/RAB22A axis regulates invasion and migration of osteosarcoma. Biomed Pharmacother. 2019;112:108695.

    Article  CAS  PubMed  Google Scholar 

  17. Shen Y, Xu J, Pan X, Zhang Y, Weng Y, Zhou D, et al. LncRNA KCNQ1OT1 sponges miR-34c-5p to promote osteosarcoma growth via ALDOA enhanced aerobic glycolysis. Cell Death Dis. 2020;11(4):278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tong CJ, Deng QC, Ou DJ, Long X, Liu H, Huang K. LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway. Aging (Albany NY). 2021;13(16):20116–30.

    Article  CAS  PubMed  Google Scholar 

  19. Zhang H, Cai Y, Zheng L, Zhang Z, Lin X, Jiang N. Long noncoding RNA NEAT1 regulate papillary thyroid cancer progression by modulating miR-129-5p/KLK7 expression. J Cell Physiol. 2018;233(10):6638–48.

    Article  CAS  PubMed  Google Scholar 

  20. Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB, Yin DD, et al. Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331–3p in gastric cancer. Mol Cancer. 2014;13:92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Xiao H, Tang K, Liu P, Chen K, Hu J, Zeng J, et al. LncRNA MALAT1 functions as a competing endogenous RNA to regulate ZEB2 expression by sponging miR-200s in clear cell kidney carcinoma. Oncotarget. 2015;6(35):38005–15.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Niu L, Zhou Y, Zhang W, Ren Y. Long noncoding RNA LINC00473 functions as a competing endogenous RNA to regulate MAPK1 expression by sponging miR-198 in breast cancer. Pathol Res Pract. 2019;215(8):152470.

    Article  CAS  PubMed  Google Scholar 

  23. Hu GD, Wang CX, Wang HY, Wang YQ, Hu S, Cao ZW, et al. Long noncoding RNA CCAT2 functions as a competitive endogenous RNA to regulate FOXC1 expression by sponging miR-23b-5p in lung adenocarcinoma. J Cell Biochem. 2019. https://doi.org/10.1002/jcb.28077.

    Article  PubMed  Google Scholar 

  24. Yu C, Sun J, Leng X, Yang J. Long noncoding RNA SNHG6 functions as a competing endogenous RNA by sponging miR-181a-5p to regulate E2F5 expression in colorectal cancer. Cancer Manag Res. 2019;11:611–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li W, Xie P, Ruan WH. Overexpression of lncRNA UCA1 promotes osteosarcoma progression and correlates with poor prognosis. J Bone Oncol. 2016;5(2):80–5.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Qi XD, Xu SY, Song Y. Prognostic value of long non-coding RNA HOST2 expression and its tumor-promotive function in human osteosarcoma. Eur Rev Med Pharmacol Sci. 2018;22(4):921–7.

    PubMed  Google Scholar 

  27. Xin X, Wu M, Meng Q, Wang C, Lu Y, Yang Y, et al. Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a. Mol Cancer. 2018;17(1):94.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Liu K, Hou Y, Liu Y, Zheng J. LncRNA SNHG15 contributes to proliferation, invasion and autophagy in osteosarcoma cells by sponging miR-141. J Biomed Sci. 2017;24(1):46.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Xu Z, Chen Q, Zeng X, Li M, Liao J. lnc-NLC1-C inhibits migration, invasion and autophagy of glioma cells by targeting miR-383 and regulating PRDX-3 expression. Oncol Lett. 2021;22(3):640.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P, et al. Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol. 2010;177(3):1459–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ye YZ, Zhang ZH, Fan XY, Xu XL, Chen ML, Chang BW, et al. Notch3 overexpression associates with poor prognosis in human non-small-cell lung cancer. Med Oncol. 2013;30(2):595.

    Article  PubMed  Google Scholar 

  32. Park JT, Li M, Nakayama K, Mao TL, Davidson B, Zhang Z, et al. Notch3 gene amplification in ovarian cancer. Cancer Res. 2006;66(12):6312–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research is supported by the General Program of Chongqing Natural Science Foundation (No. cstc2019jcyj-msxmX0447) the National Natural Science Foundation of China (Project no.81972519), and Chongqing Research Program of Basic Research and Frontier Technology (no. cstc2019jcyj-msxm1073).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xue-feng Tang or Qiao-nan Guo.

Ethics declarations

Conflict of interest

All authors declare there are no conflict of interest.

Ethical approval

The human study was approved by the the Medical Ethics Committee of Second Affiliated Hospital of Army Medical University (approval number:2018-069-01). The animal study was approved by the Laboratory Animal Welfare and Ethics Committee Of the Army Medical University (approval number: AMUWEC2019178) and followed the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 802 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, JY., Lv, Yf., Cao, Y. et al. Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p. Human Cell 36, 2140–2151 (2023). https://doi.org/10.1007/s13577-023-00958-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-023-00958-8

Keywords

Navigation