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The role of long non-coding RNA BCAR4 in human cancers

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Abstract

Long non-coding RNA (lncRNA) is a type of non-coding RNA with length of nucleotides > 200 bp. Increasing evidences show that lncRNA breast cancer antiestrogen resistance 4 (BCAR4) plays an important role in the occurrence and development of various human cancers. It is found that BCAR4 is highly expressed in diverse tumor tissues and cells, and the high expression of BCAR4 is usually associated with poor prognosis. BCAR4 is considered as an oncogene in human cancers. By competing endogenous RNA (ceRNA) mechanism and regulating different signaling pathways, BCAR4 participates in the proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition (EMT), metastasis and tumorigenesis of different cancers. In addition, overexpression of BCAR4 promotes drug resistance of tumor cells. Therefore, BCAR4 is a promising biomarker for cancer diagnosis and prognosis, and it is a potential target for cancer therapy. This paper reviews studies focusing on the relationship between BCAR4 and cancers in recent years and aims to summarize the effect and mechanism of BCAR4 in human cancers.

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References

  1. Li Z, Shen J, Chan MT, Wu WK. TUG1: a pivotal oncogenic long non-coding RNA of human cancers. Cell Prolif. 2016;49(4):471–5. https://doi.org/10.1111/cpr.12269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sun Q, Tripathi V, Yoon JH, Singh DK, Hao Q, Min KW, et al. MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs. Nucleic Acids Res. 2018;46(19):10405–16. https://doi.org/10.1093/nar/gky696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zhang J, Wang P, Wan L, Xu S, Pang D. The emergence of noncoding RNAs as heracles in autophagy. Autophagy. 2017;13(6):1004–24. https://doi.org/10.1080/15548627.2017.1312041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schmitz SU, Grote P, Herrmann BG. Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 2016;73(13):2491–509. https://doi.org/10.1007/s00018-016-2174-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zou A, Liu R, Wu X. Long non-coding RNA MALAT1 is up-regulated in ovarian cancer tissue and promotes SK-OV-3 cell proliferation and invasion. Neoplasma. 2016;63(6):865–72. https://doi.org/10.4149/neo_2016_605.

    Article  CAS  PubMed  Google Scholar 

  6. Xia H, Chen Q, Chen Y, Ge X, Leng W, Tang Q, et al. The lncRNA MALAT1 is a novel biomarker for gastric cancer metastasis. Oncotarget. 2016;7(35):56209–18. https://doi.org/10.18632/oncotarget.10941.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dong Y, Liang G, Yuan B, Yang C, Gao R, Zhou X. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(3):1477–86. https://doi.org/10.1007/s13277-014-2631-4.

    Article  CAS  Google Scholar 

  8. Ji J, Tang J, Deng L, Xie Y, Jiang R, Li G, et al. LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway. Oncotarget. 2015;6(40):42813–24. https://doi.org/10.18632/oncotarget.5970.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhao JH, Sun JX, Song YX, Chen XW, Yang YC, Ma B, et al. A novel long noncoding RNA-LOWEG is low expressed in gastric cancer and acts as a tumor suppressor by inhibiting cell invasion. J Cancer Res Clin Oncol. 2016;142(3):601–9. https://doi.org/10.1007/s00432-015-2071-6.

    Article  CAS  PubMed  Google Scholar 

  10. Kunej T, Obsteter J, Pogacar Z, Horvat S, Calin GA. The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring. Crit Rev Clin Lab Sci. 2014;51(6):344–57. https://doi.org/10.3109/10408363.2014.944299.

    Article  CAS  PubMed  Google Scholar 

  11. Xu B, Konze KD, Jin J, Wang GG. Targeting EZH2 and PRC2 dependence as novel anticancer therapy. Exp Hematol. 2015;43(8):698–712. https://doi.org/10.1016/j.exphem.2015.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guo S, Zhang L, Zhang Y, Wu Z, He D, Li X, et al. Long non-coding RNA TUG1 enhances chemosensitivity in non-small cell lung cancer by impairing microRNA-221-dependent PTEN inhibition. Aging. 2019;11(18):7553–69. https://doi.org/10.18632/aging.102271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meijer D, van Agthoven T, Bosma PT, Nooter K, Dorssers LC. Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells. Mol Cancer Res. 2006;4(6):379–86. https://doi.org/10.1158/1541-7786.Mcr-05-0156.

    Article  CAS  PubMed  Google Scholar 

  14. Godinho MF, Sieuwerts AM, Look MP, Meijer D, Foekens JA, Dorssers LC, et al. Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer. Br J Cancer. 2010;103(8):1284–91. https://doi.org/10.1038/sj.bjc.6605884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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. https://doi.org/10.3322/caac.21660.

    Article  PubMed  Google Scholar 

  16. van Agthoven T, Dorssers LC, Lehmann U, Kreipe H, Looijenga LH, Christgen M. Breast cancer anti-estrogen resistance 4 (BCAR4) drives proliferation of IPH-926 lobular carcinoma cells. PLoS ONE. 2015;10(8):e0136845. https://doi.org/10.1371/journal.pone.0136845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xing Z, Lin A, Li C, Liang K, Wang S, Liu Y, et al. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell. 2014;159(5):1110–25. https://doi.org/10.1016/j.cell.2014.10.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li F, Miao L, Xue T, Qin H, Mondal S, Thompson PR, et al. Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells. J Exp Clin Cancer Res CR. 2019;38(1):414. https://doi.org/10.1186/s13046-019-1404-8.

    Article  PubMed  Google Scholar 

  19. Godinho M, Meijer D, Setyono-Han B, Dorssers LC, van Agthoven T. Characterization of BCAR4, a novel oncogene causing endocrine resistance in human breast cancer cells. J Cell Physiol. 2011;226(7):1741–9. https://doi.org/10.1002/jcp.22503.

    Article  CAS  PubMed  Google Scholar 

  20. Godinho MF, Wulfkuhle JD, Look MP, Sieuwerts AM, Sleijfer S, Foekens JA, et al. BCAR4 induces antioestrogen resistance but sensitises breast cancer to lapatinib. Br J Cancer. 2012;107(6):947–55. https://doi.org/10.1038/bjc.2012.351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chou AJ, Geller DS, Gorlick R. Therapy for osteosarcoma: where do we go from here? Paediatr Drugs. 2008;10(5):315–27. https://doi.org/10.2165/00148581-200810050-00005.

    Article  PubMed  Google Scholar 

  22. Chen F, Mo J, Zhang L. Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription. Tumour Biol J Int Soc Oncodev Biol Med. 2016;37(10):13403–12. https://doi.org/10.1007/s13277-016-5256-y.

    Article  CAS  Google Scholar 

  23. Ju L, Zhou YM, Yang GS. Up-regulation of long non-coding RNA BCAR4 predicts a poor prognosis in patients with osteosarcoma, and promotes cell invasion and metastasis. Eur Rev Med Pharmacol Sci. 2016;20(21):4445–51.

    CAS  PubMed  Google Scholar 

  24. Li Y, Li G, Guo X, Yao H, Wang G, Li C. Non-coding RNA in bladder cancer. Cancer Lett. 2020;485:38–44. https://doi.org/10.1016/j.canlet.2020.04.023.

    Article  CAS  PubMed  Google Scholar 

  25. Wang X, He H, Rui W, Xie X, Wang D, Zhu Y. Long non-coding RNA BCAR4 binds to miR-644a and targets TLX1 to promote the progression of bladder cancer. Onco Targets Ther. 2020;13:2483–90. https://doi.org/10.2147/ott.S232965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang R, Wang J, Jia E, Zhang J, Liu N, Chi C. lncRNA BCAR4 sponges miR-370-3p to promote bladder cancer progression via Wnt signaling. Int J Mol Med. 2020;45(2):578–88. https://doi.org/10.3892/ijmm.2019.4444.

    Article  CAS  PubMed  Google Scholar 

  27. Garg M, Maurya N. WNT/β-catenin signaling in urothelial carcinoma of bladder. World J Nephrol. 2019;8(5):83–94. https://doi.org/10.5527/wjn.v8.i5.83.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Durinck K, Van Loocke W, Van der Meulen J, Van de Walle I, Ongenaert M, Rondou P, et al. Characterization of the genome-wide TLX1 binding profile in T cell acute lymphoblastic leukemia. Leukemia. 2015;29(12):2317–27. https://doi.org/10.1038/leu.2015.162.

    Article  CAS  PubMed  Google Scholar 

  29. Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1211–8. https://doi.org/10.1038/ng.3909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhu X, Chen L, Liu L, Niu X. EMT-mediated acquired EGFR-TKI resistance in NSCLC: mechanisms and strategies. Front Oncol. 2019;9:1044. https://doi.org/10.3389/fonc.2019.01044.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Li N, Gao WJ, Liu NS. LncRNA BCAR4 promotes proliferation, invasion and metastasis of non-small cell lung cancer cells by affecting epithelial-mesenchymal transition. Eur Rev Med Pharmacol Sci. 2017;21(9):2075–86.

    CAS  PubMed  Google Scholar 

  32. Gong J, Zhang H, He L, Wang L, Wang J. Increased expression of long non-coding RNA BCAR4 is predictive of poor prognosis in patients with non-small cell lung cancer. Tohoku J Exp Med. 2017;241(1):29–34. https://doi.org/10.1620/tjem.241.29.

    Article  CAS  PubMed  Google Scholar 

  33. Yang H, Yan L, Sun K, Sun X, Zhang X, Cai K, et al. lncRNA BCAR4 increases viability, invasion, and migration of non-small cell lung cancer cells by targeting glioma-associated oncogene 2 (GLI2). Oncol Res. 2019;27(3):359–69. https://doi.org/10.3727/096504018x15220594629967.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ayoub WS, Steggerda J, Yang JD, Kuo A, Sundaram V, Lu SC. Current status of hepatocellular carcinoma detection: screening strategies and novel biomarkers. Ther Adv Med Oncol. 2019;11:1758835919869120. https://doi.org/10.1177/1758835919869120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhang Y, Zhou H. LncRNA BCAR4 promotes liver cancer progression by upregulating ANAPC11 expression through sponging miR-1261. Int J Mol Med. 2020;46(1):159–66. https://doi.org/10.3892/ijmm.2020.4586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang A, Meng J, Liu H, Li C, Zhou Z. Long non-coding RNA BCAR4 promotes liver cancer progression by regulating proliferation, migration and invasion. Oncol Lett. 2020;20(3):2779–87. https://doi.org/10.3892/ol.2020.11826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shi YJ, Huo KK. Knockdown expression of Apc11 leads to cell-cycle distribution reduction in G2/M phase. Genet Mol Res. 2012;11(3):2814–22. https://doi.org/10.4238/2012.August.24.6.

    Article  CAS  PubMed  Google Scholar 

  38. Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007;370(9590):890–907. https://doi.org/10.1016/s0140-6736(07)61416-0.

    Article  CAS  PubMed  Google Scholar 

  39. Zou R, Chen X, Jin X, Li S, Ou R, Xue J, et al. Up-regulated BCAR4 contributes to proliferation and migration of cervical cancer cells. Surg Oncol. 2018;27(2):306–13. https://doi.org/10.1016/j.suronc.2018.05.013.

    Article  PubMed  Google Scholar 

  40. Sampson JH, Gunn MD, Fecci PE, Ashley DM. Brain immunology and immunotherapy in brain tumours. Nat Rev Cancer. 2020;20(1):12–25. https://doi.org/10.1038/s41568-019-0224-7.

    Article  CAS  PubMed  Google Scholar 

  41. Wang Z, Wang L, Liang Z, Xi Y. Long non-coding RNA BCAR4 promotes growth, invasion and tumorigenicity by targeting miR-2276 to upregulate MMP7 expression in glioma. Onco Targets Ther. 2019;12:10963–73. https://doi.org/10.2147/ott.S226026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Wei L, Yi Z, Guo K, Long X. Long noncoding RNA BCAR4 promotes glioma cell proliferation via EGFR/PI3K/AKT signaling pathway. J Cell Physiol. 2019;234(12):23608–17. https://doi.org/10.1002/jcp.28929.

    Article  CAS  PubMed  Google Scholar 

  43. Orangio GR. The economics of colon cancer. Surg Oncol Clin N Am. 2018;27(2):327–47. https://doi.org/10.1016/j.soc.2017.11.007.

    Article  PubMed  Google Scholar 

  44. Ouyang S, Zheng X, Zhou X, Chen Z, Yang X, Xie M. LncRNA BCAR4 promotes colon cancer progression via activating Wnt/β-catenin signaling. Oncotarget. 2017;8(54):92815–26. https://doi.org/10.18632/oncotarget.21590.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gupta R, Bhatt LK, Johnston TP, Prabhavalkar KS. Colon cancer stem cells: potential target for the treatment of colorectal cancer. Cancer Biol Ther. 2019;20(8):1068–82. https://doi.org/10.1080/15384047.2019.1599660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, et al. Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol Rev. 2012;64(3):520–39. https://doi.org/10.1124/pr.111.005538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ouyang S, Zhou X, Chen Z, Wang M, Zheng X, Xie M. LncRNA BCAR4, targeting to miR-665/STAT3 signaling, maintains cancer stem cells stemness and promotes tumorigenicity in colorectal cancer. Cancer Cell Int. 2019;19:72. https://doi.org/10.1186/s12935-019-0784-3.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Galoczova M, Coates P, Vojtesek B. STAT3, stem cells, cancer stem cells and p63. Cell Mol Biol Lett. 2018;23:12. https://doi.org/10.1186/s11658-018-0078-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wang L, Chunyan Q, Zhou Y, He Q, Ma Y, Ga Y, et al. BCAR4 increase cisplatin resistance and predicted poor survival in gastric cancer patients. Eur Rev Med Pharmacol Sci. 2017;21(18):4064–70.

    CAS  PubMed  Google Scholar 

  50. Zhou GR, Huang DP, Sun ZF, Zhang XF. Long non-coding RNA BCAR4 accelerates cell proliferation and suppresses cell apoptosis in gastric cancer via regulating MAPK/ERK signaling. Eur Rev Med Pharmacol Sci. 2020;24(7):3657–64. https://doi.org/10.26355/eurrev_202004_20828.

    Article  PubMed  Google Scholar 

  51. Biagioni A, Skalamera I, Peri S, Schiavone N, Cianchi F, Giommoni E, et al. Update on gastric cancer treatments and gene therapies. Cancer Metastasis Rev. 2019;38(3):537–48. https://doi.org/10.1007/s10555-019-09803-7.

    Article  PubMed  Google Scholar 

  52. Phi LTH, Sari IN, Yang YG, Lee SH, Jun N, Kim KS, et al. Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int. 2018;2018:5416923. https://doi.org/10.1155/2018/5416923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Roos E, van Coevorden F, Verhoef C, Wouters MW, Kroon HM, Hogendoorn PC, et al. Prognosis of primary and recurrent chondrosarcoma of the rib. Ann Surg Oncol. 2016;23(3):811–7. https://doi.org/10.1245/s10434-015-4932-2.

    Article  PubMed  Google Scholar 

  54. Shui X, Zhou C, Lin W, Yu Y, Feng Y, Kong J. Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway. Exp Biol Med (Maywood). 2017;242(10):1044–50. https://doi.org/10.1177/1535370217700735.

    Article  CAS  Google Scholar 

  55. Vlachostergios PJ, Puca L, Beltran H. Emerging variants of castration-resistant prostate cancer. Curr Oncol Rep. 2017;19(5):32. https://doi.org/10.1007/s11912-017-0593-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cai Z, Wu Y, Li Y, Ren J, Wang L. BCAR4 activates GLI2 signaling in prostate cancer to contribute to castration resistance. Aging. 2018;10(12):3702–12. https://doi.org/10.18632/aging.101664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chandrasekar T, Yang JC, Gao AC, Evans CP. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol. 2015;4(3):365–80. https://doi.org/10.3978/j.issn.2223-4683.2015.05.02.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Zhao W, Wang Z, Fang X, Li N, Fang J. Long noncoding RNA Breast cancer antiestrogen resistance 4 is associated with cancer progression and its significant prognostic value. J Cell Physiol. 2019;234(8):12956–63. https://doi.org/10.1002/jcp.27962.

    Article  CAS  PubMed  Google Scholar 

  59. Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Cancer Res. 2017;77(15):3965–81. https://doi.org/10.1158/0008-5472.Can-16-2634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kazimierczyk M, Kasprowicz MK, Kasprzyk ME, Wrzesinski J. Human long noncoding RNA interactome: detection, characterization and function. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21031027.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the The National Natural Science Foundation of China (81874017, 81960403, 82060405 and 82060413); Natrual Science Foundation of Gansu Province of China (20JR5RA320); Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (CY2017-ZD02, CY2017-QN12).

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  1. Qiong Yi and Zhongcheng Liu contributed equally to this work and should be considered as co-first authors.

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  1. Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China

    Qiong Yi, Zhongcheng Liu, Kun Zhang, Xuening Liu, Lifu Wang, Bin Geng & Yayi Xia

  2. Orthopaedics Key Laboratory of Gansu Province, Lanzhou, 730000, Gansu, China

    Qiong Yi, Zhongcheng Liu, Kun Zhang, Xuening Liu, Lifu Wang, Bin Geng & Yayi Xia

  3. Orthopaedic Clinical Medical Research Center of Gansu Province, Lanzhou, 730000, Gansu, China

    Qiong Yi, Zhongcheng Liu, Kun Zhang, Xuening Liu, Lifu Wang, Bin Geng & Yayi Xia

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QY and ZL contributed to the plan, writing, production and proofreading of this paper. KZ, XL and LW contributed to discussing the data and text. BG and YX participated in its critical review of the manuscript. All authors also participated in the data access and final typesetting. All authors read and approved the final manuscript.

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Yi, Q., Liu, Z., Zhang, K. et al. The role of long non-coding RNA BCAR4 in human cancers. Human Cell 34, 1301–1309 (2021). https://doi.org/10.1007/s13577-021-00556-6

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