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LncRNA DANCR regulates the growth and metastasis of oral squamous cell carcinoma cells via altering miR-216a-5p expression

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Abstract

The study aims to investigate how DANCR can alter the growth and metastasis of oral squamous cell carcinoma (OSCC) cells by regulating miR-216a-5p. The expression of DANCR and miR-216a-5p in OSCC patients and cells were measured. SCC15 and CAL-27 cells were selected to divide into Control, sh-NC, DANCR shRNA, DANCR, miR-216a-5p mimic, and DANCR + miR-216a-5p mimic groups. Dual-luciferase reporter gene assay was performed for the verification of the targeting relationship between miR-216a-5p and DANCR/Bcl-2/KLF12. We also quantified the abilities of OSCC cells regarding proliferation, invasion, migration and apoptosis, and the expression levels of apoptosis-related proteins were measured. Finally, the tumor-bearing nude mice were established to verify the effect of DANCR in vivo. Up-regulated DANCR expression and down-regulated miR-216a-5p expression were observed in both OSCC tissues and cells, and they were proven strongly correlated to the histological grade, clinical staging and lymph node metastasis of OSCC patients. Dual-luciferase reporter gene assay showed a target relationship between DANCR and miR-216a-5p, as well as between miR-216a-5p and Bcl-2/KLF12. Both DANCR shRNA and miR-216a-5p mimic decreased proliferative, migration and invasive abilities of OSCC cells with increased cell apoptosis. However, DANCR group showed completely opposite trends. Moreover, miR-216a-5p mimic could reverse the role of DANCR in promoting tumor growth. In-vivo experiment confirmed the inhibitory role of DANCR shRNA in tumor growth and metastasis. We concluded that DANCR may promote the growth and metastasis of OSCC cells and suppress OSCC cell apoptosis by sponging miR-216a-5p.

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References

  1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16.

    Article  Google Scholar 

  2. Shiah SG, Hsiao JR, Chang WM, et al. Downregulated miR329 and miR410 promote the proliferation and invasion of oral squamous cell carcinoma by targeting Wnt-7b. Cancer Res. 2014;74:7560–72.

    Article  CAS  Google Scholar 

  3. Marur S, Forastiere AA. Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016;91:386–96.

    Article  Google Scholar 

  4. Brocklehurst PR, Baker SR, Speight PM. Oral cancer screening: what have we learnt and what is there still to achieve? Future Oncol. 2010;6:299–304.

    Article  Google Scholar 

  5. Yang YT, Wang YF, Lai JY, et al. Long non-coding RNA UCA1 contributes to the progression of oral squamous cell carcinoma by regulating the WNT/beta-catenin signaling pathway. Cancer Sci. 2016;107:1581–9.

    Article  CAS  Google Scholar 

  6. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.

    Article  CAS  Google Scholar 

  7. Cao MX, Jiang YP, Tang YL, Liang XH. The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity. Oncotarget. 2017;8:12472–83.

    Article  Google Scholar 

  8. Kretz M, Webster DE, Flockhart RJ, et al. Suppression of progenitor differentiation requires the long noncoding RNA ANCR. Genes Dev. 2012;26:338–43.

    Article  CAS  Google Scholar 

  9. Wang JX, Yang Y, Li K. Long noncoding RNA DANCR aggravates retinoblastoma through miR-34c and miR-613 by targeting MMP-9. J Cell Physiol. 2018;233:6986–95.

    Article  CAS  Google Scholar 

  10. Wang Y, Lu Z, Wang N, et al. Long noncoding RNA DANCR promotes colorectal cancer proliferation and metastasis via miR-577 sponging. Exp Mol Med. 2018;50:57.

    CAS  PubMed Central  Google Scholar 

  11. Chai L, Yang G. MiR-216a-5p targets TCTN1 to inhibit cell proliferation and induce apoptosis in esophageal squamous cell carcinoma. Cell Mol Biol Lett. 2019;24:46.

    Article  Google Scholar 

  12. Li L, Ma HQ. MicroRNA-216a inhibits the growth and metastasis of oral squamous cell carcinoma by targeting eukaryotic translation initiation factor 4B. Mol Med Rep. 2015;12:3156–62.

    Article  CAS  Google Scholar 

  13. Ma J, Liu J, Lu C, Cai D. Pachymic acid induces apoptosis via activating ROS-dependent JNK and ER stress pathways in lung cancer cells. Cancer Cell Int. 2015;15:78.

    Article  Google Scholar 

  14. Deng G, Zeng S, Ma J, et al. The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma. Sci Rep. 2017;7:41616.

    Article  CAS  Google Scholar 

  15. Jiang F, Zhou JY, Zhang D, Liu MH, Chen YG. Artesunate induces apoptosis and autophagy in HCT116 colon cancer cells, and autophagy inhibition enhances the artesunateinduced apoptosis. Int J Mol Med. 2018;42:1295–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu Y, Zhang M, Liang L, Li J, Chen YX. Over-expression of lncRNA DANCR is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 2015;8:11480–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hao YP, Qiu JH, Zhang DB, Yu CG. Long non-coding RNA DANCR, a prognostic indicator, promotes cell growth and tumorigenicity in gastric cancer. Tumour Biol. 2017;39:1010428317699798.

    Article  Google Scholar 

  18. Xu D, Yu J, Gao G, Lu G, Zhang Y, Ma P. LncRNA DANCR functions as a competing endogenous RNA to regulate RAB1A expression by sponging miR-634 in glioma. Biosci Rep. 2018. https://doi.org/10.1042/BSR20171664.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tao Y, Yang S, Wu Y, et al. MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting JAK2/STAT3-mediated EMT process. Oncotarget. 2017;8:88870–81.

    Article  Google Scholar 

  20. Liu Q, Guo X, Que S, et al. LncRNA RSU1P2 contributes to tumorigenesis by acting as a ceRNA against let-7a in cervical cancer cells. Oncotarget. 2017;8:43768–81.

    Article  Google Scholar 

  21. Lu QC, Rui ZH, Guo ZL, Xie W, Shan S, Ren T. LncRNA-DANCR contributes to lung adenocarcinoma progression by sponging miR-496 to modulate mTOR expression. J Cell Mol Med. 2018;22:1527–37.

    Article  CAS  Google Scholar 

  22. Zhan Y, Chen Z, Li Y, et al. Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA. J Exp Clin Cancer Res. 2018;37:273.

    Article  CAS  Google Scholar 

  23. Wang S, Jiang M. The long non-coding RNA-DANCR exerts oncogenic functions in non-small cell lung cancer via miR-758-3p. Biomed Pharmacother. 2018;103:94–100.

    Article  CAS  Google Scholar 

  24. Yang B, Gao G, Wang Z, et al. Long non-coding RNA HOTTIP promotes prostate cancer cells proliferation and migration by sponging miR-216a-5p. Biosci Rep. 2018. https://doi.org/10.1042/BSR20180566.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chang L, Zhao D, Liu HB, et al. Activation of sonic hedgehog signaling enhances cell migration and invasion by induction of matrix metalloproteinase-2 and -9 via the phosphoinositide-3 kinase/AKT signaling pathway in glioblastoma. Mol Med Rep. 2015;12:6702–10.

    Article  CAS  Google Scholar 

  26. Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013;14:32.

    Article  CAS  Google Scholar 

  27. Chen DL, Engle JT, Griffin EA, et al. Imaging caspase-3 activation as a marker of apoptosis-targeted treatment response in cancer. Mol Imaging Biol. 2015;17:384–93.

    Article  Google Scholar 

  28. Garner TP, Lopez A, Reyna DE, Spitz AZ, Gavathiotis E. Progress in targeting the BCL-2 family of proteins. Curr Opin Chem Biol. 2017;39:133–42.

    Article  CAS  Google Scholar 

  29. Sharifi AM, Hoda FE, Noor AM. Studying the effect of LPS on cytotoxicity and apoptosis in PC12 neuronal cells: role of Bax, Bcl-2, and Caspase-3 protein expression. Toxicol Mech Methods. 2010;20:316–20.

    Article  CAS  Google Scholar 

  30. Tan C, Dlugosz PJ, Peng J, et al. Auto-activation of the apoptosis protein Bax increases mitochondrial membrane permeability and is inhibited by Bcl-2. J Biol Chem. 2006;281:14764–75.

    Article  CAS  Google Scholar 

  31. Guo J, Zhang K, Ji Y, Jiang X, Zuo S. Effects of ethyl pyruvate on myocardial apoptosis and expression of Bcl-2 and Bax proteins after ischemia-reperfusion in rats. J Huazhong Univ Sci Technolog Med Sci. 2008;28:281–3.

    Article  Google Scholar 

  32. Shi H, Shi J, Zhang Y, et al. Long non-coding RNA DANCR promotes cell proliferation, migration, invasion and resistance to apoptosis in esophageal cancer. J Thorac Dis. 2018;10:2573–82.

    Article  Google Scholar 

  33. Sun Y, Hu B, Wang Y, et al. miR-216a-5p inhibits malignant progression in small cell lung cancer: involvement of the Bcl-2 family proteins. Cancer Manag Res. 2018;10:4735–45.

    Article  CAS  Google Scholar 

  34. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141:52–67.

    Article  CAS  Google Scholar 

  35. Ding L, Ding Y, Kong X, et al. Dysregulation of Kruppel-like factor 12 in the development of endometrial cancer. Gynecol Oncol. 2019;152:177–84.

    Article  CAS  Google Scholar 

  36. Wang J, Pu J, Zhang Y, et al. DANCR contributed to hepatocellular carcinoma malignancy via sponging miR-216a-5p and modulating KLF12. J Cell Physiol. 2019;234:9408–16.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all the reviewers in this work.

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Authors and Affiliations

  1. Department of Orthodontics, Dongfeng Stomatological Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province, China

    Xing-Hui Qu, You-Ling Shi, Yan Ma, Wei-Wei Bao & Lei Yang

  2. Department of Oral Surgery, Dongfeng Stomatological Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei Province, China

    Jin-Chao Li

  3. Department of Pediatric Dentistry, Dongfeng Stomatological Hospital, Hubei University of Medicine, No. 16, Daling Road, Zhangwan District, Shiyan, 442000, Hubei Province, China

    Fan Zhang

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  1. Xing-Hui Qu
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Correspondence to Fan Zhang.

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Approval was obtained from the Ethics Committee of our hospital prior to the study. And all animal experiments were performed in full compliance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85-23, 1996), with the approval of Medical Ethics Committee of our academy.

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Qu, XH., Shi, YL., Ma, Y. et al. LncRNA DANCR regulates the growth and metastasis of oral squamous cell carcinoma cells via altering miR-216a-5p expression. Human Cell 33, 1281–1293 (2020). https://doi.org/10.1007/s13577-020-00411-0

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