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Cancer gene therapy
09, 2021;28 (9): 1025-1034.

LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression.

Chuandong Cheng, Yongfei Dong, Xiaoyu Ru, Yanghua Xia, Ying Ji
Author Information
  1. Chuandong Cheng: High Magnetic Field Laboratory, Chinese Academy of Sciences, Mailbox 1110, 350 Shushanhu Road, Hefei, Anhui, 230031, P. R. China.
  2. Yongfei Dong: Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China.
  3. Xiaoyu Ru: Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China.
  4. Yanghua Xia: Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China. XXXiayanghua@163.com.
  5. Ying Ji: Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China. Jiying201911@163.com. ORCID
PMID: 33293663 DOI: 10.1038/s41417-020-00263-8

Abstract

Recently, the role of long noncoding RNA (lncRNA) has been identified in human diseases, and we aim to explore the role of lncRNA antidifferentiation noncoding RNA (ANCR) in glioma. Expression of lncRNA ANCR, enhancer of zeste homolog 2 (EZH2), and phosphatase and tensin homolog (PTEN) in glioma tissues and cells was determined by RT-PCR or western blot assay. The correlation between expression of ANCR, EZH2, and PTEN in glioma tissues was analyzed using Pearson test. The apoptosis, transwell invasion, migration, colony formation, and proliferation assays were conducted to evaluate the influences of lncRNA ANCR depletion, EZH2 reduction, or PTEN elevation on the cell biology of glioma cells. The relationships between ANCR and EZH2, and between EZH2 and PTEN were confirmed through RIP, RNA pull-down, and chromatin immunoprecipitation assays. Our results indicated that ANCR and EZH2 were upregulated and PTEN was downregulated in glioma tissues and cell lines. ANCR expression was positively related to EZH2 expression, while PTEN expression was negatively related to ANCR/EZH2 expression. Inhibited ANCR, reduced EZH2, or elevated PTEN could reduce the ability of invasion, migration, and proliferation, and promote apoptosis of glioma cells. PTEN overexpression or EZH2 inhibition reversed the promotive role of ANCR upregulation in glioma cell growth and metastasis. Mechanistically, PTEN was upregulated in ANCR knockdown glioma cells. EZH2 interacted with ANCR in glioma cells. In conclusion, we have found that restrained ANCR could repress invasion, migration, and proliferation, as well as promote apoptosis of glioma cells through interacting with EZH2 and regulating the expression of PTEN, offering an effective therapeutic target for patients with glioma.

References

  1. Huang S, Zheng S, Huang S, Cheng H, Lin Y, Wen Y, et al. Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma. Artif Cells Nanomed Biotechnol. 2019;47:250–5. [DOI: 10.1080/21691401.2018.1549062]
  2. Liang X, Dong Z, Bin W, Dekang N, Xuhang Z, Shuyuan Z, et al. PAX3 promotes proliferation of human glioma cells by WNT/beta-catenin signaling pathways. J Mol Neurosci. 2019;68:66–77. [DOI: 10.1007/s12031-019-01283-2]
  3. Pandey JP, Kaur N, Costa S, Amorim J, Nabico R, Linhares P, et al. Immunoglobulin genes implicated in glioma risk. Oncoimmunology. 2014;3:e28609. [DOI: 10.4161/onci.28609]
  4. Su H, Zou D, Sun Y, Dai Y. Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p. Cell Mol Biol Lett. 2019;24:24. [DOI: 10.1186/s11658-019-0149-x]
  5. Niu WX, Zhou CX, Cheng CD, Bao DJ, Dong YF, Li DX, et al. Effects of lentivirus-mediated CYP17A1 gene silencing on the biological activity of glioma. Neurosci Lett. 2019;692:210–5. [DOI: 10.1016/j.neulet.2018.11.017]
  6. Yang G, Lu X, Yuan L. LncRNA: a link between RNA and cancer. Biochim Biophys Acta. 2014;1839:1097–109. [DOI: 10.1016/j.bbagrm.2014.08.012]
  7. Li, Q, Q Wu, Z Li, Y Hu, F Zhou, Z Zhai, et al. LncRNA LINC00319 is associated with tumorigenesis and poor prognosis in glioma. Eur J Pharmacol. 2019;861:172556.
  8. Chen, Y, C Bao, X Zhang, X Lin, H Huang, and Z Wang. Long non-coding RNA HCG11 modulates glioma progression through cooperating with miR-496/CPEB3 axis. Cell Prolif. 2019;52:e12615.
  9. Li Q, Zhang Z, Guo S, Tang G, Lu W, Qi X. LncRNA ANCR is positively correlated with transforming growth factor-beta1 in patients with osteoarthritis. J Cell Biochem. 2019;120:14226–32. [DOI: 10.1002/jcb.28881]
  10. Li Z, Dong M, Fan D, Hou P, Li H, Liu L, et al. LncRNA ANCR down-regulation promotes TGF-beta-induced EMT and metastasis in breast cancer. Oncotarget. 2017;8:67329–43. [DOI: 10.18632/oncotarget.18622]
  11. Wang S, Lan F, Xia Y. lncRA ANCR inhibits non-small cell lung cancer cell migration and invasion by inactivating TGF-beta pathway. Med Sci Monit. 2018;24:6002–9. [DOI: 10.12659/MSM.911492]
  12. Malakootian M, Mirzadeh Azad F, Fouani Y, Taheri Bajgan E, Saberi H, Mowla SJ. Anti-differentiation non-coding RNA, ANCR, is differentially expressed in different types of brain tumors. J Neurooncol. 2018;138:261–70. [DOI: 10.1007/s11060-018-2809-5]
  13. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012;492:108–12. [DOI: 10.1038/nature11606]
  14. Yang, A, H Wang, and X Yang. Long non-coding RNA PVT1 indicates a poor prognosis of glioma and promotes cell proliferation and invasion via target EZH2. Biosci Rep. 2017;37:BSR20170871.
  15. Lu J, Ji H, Tang H, Xu Z. microRNA-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant cell proliferation in human glioma. Biochem Biophys Res Commun. 2018;503:1610–7. [DOI: 10.1016/j.bbrc.2018.07.089]
  16. Zhang Y, Yu X, Chen L, Zhang Z, Feng S. EZH2 overexpression is associated with poor prognosis in patients with glioma. Oncotarget. 2017;8:565–73. [DOI: 10.18632/oncotarget.13478]
  17. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96. [DOI: 10.1038/nrm3330]
  18. Liu C, Wu H, Li Y, Shen L, Yu R, Yin H, et al. SALL4 suppresses PTEN expression to promote glioma cell proliferation via PI3K/AKT signaling pathway. J Neurooncol. 2017;135:263–72. [DOI: 10.1007/s11060-017-2589-3]
  19. Ma Q, Zhang Y, Meng R, Xie KM, Xiong Y, Lin S, et al. MAGI3 suppresses glioma cell proliferation via upregulation of PTEN expression. Biomed Environ Sci. 2015;28:502–9. [PMID: 26248734]
  20. Zhang F, Peng H. LncRNA-ANCR regulates the cell growth of osteosarcoma by interacting with EZH2 and affecting the expression of p21 and p27. J Orthop Surg Res. 2017;12:103. [DOI: 10.1186/s13018-017-0599-7]
  21. Ma X, Zhou J, Liu J, Wu G, Yu Y, Zhu H, et al. LncRNA ANCR promotes proliferation and radiation resistance of nasopharyngeal carcinoma by inhibiting PTEN expression. OncoTargets Ther. 2018;11:8399–408. [DOI: 10.2147/OTT.S182573]
  22. Thurnher MM. 2007 World Health Organization classification of tumours of the central nervous system. Cancer Imaging. 2009;9:S1–3. [DOI: 10.1102/1470-7330.2009.9001]
  23. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, et al. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 1999;59:5830–5. [PMID: 10582706]
  24. Tuo YL, Li XM, Luo J. Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through decreasing tumor suppressive miR-143. Eur Rev Med Pharm Sci. 2015;19:3403–11.
  25. Liu YD, Liu LP. Circ100284 promotes invasion and migration of osteosarcoma cells by down-regulating PTEN and EMP1. Eur Rev Med Pharm Sci. 2020;24:6540–50.
  26. Zhou H, Ma Y, Zhong D, Yang L. Knockdown of lncRNA HOXD-AS1 suppresses proliferation, migration and invasion and enhances cisplatin sensitivity of glioma cells by sponging miR-204. Biomed Pharmacother. 2019;112:108633. [DOI: 10.1016/j.biopha.2019.108633]
  27. Chen X, Yan GY. Novel human lncRNA-disease association inference based on lncRNA expression profiles. Bioinformatics. 2013;29:2617–24. [DOI: 10.1093/bioinformatics/btt426]
  28. Chen J, Zhang M, Zhang X, Fan L, Liu P, Yu L, et al. EZH2 inhibitor DZNep modulates microglial activation and protects against ischaemic brain injury after experimental stroke. Eur J Pharm. 2019;857:172452. [DOI: 10.1016/j.ejphar.2019.172452]
  29. Wang J, Liu Z, Cui Y, Liu Y, Fang J, Xu L, et al. Evaluation of EZH2 expression, BRAF V600E mutation, and CDKN2A/B deletions in epithelioid glioblastoma and anaplastic pleomorphic xanthoastrocytoma. J Neurooncol. 2019;144:137–46. [DOI: 10.1007/s11060-019-03212-0]
  30. Bao, L and X Li. MicroRNA-32 targeting PTEN enhances M2 macrophage polarization in the glioma microenvironment and further promotes the progression of glioma. Mol Cell Biochem. 2019;460:67–79.
  31. Zhu Y, Liu B, Zhang P, Zhang J, Wang L. LncRNA TUSC8 inhibits the invasion and migration of cervical cancer cells via miR-641/PTEN axis. Cell Biol Int. 2019;43:781–8. [DOI: 10.1002/cbin.11152]
  32. Zhang XS, Hu YH, Gao HY, Lan XW, Xue YW. Downregulation of Notch1 inhibits the invasion and metastasis of human gastric cancer cells SGC7901 and MKN74 in vitro through PTEN activation and dephosphorylation of Akt and FAK. Mol Med Rep. 2017;16:2318–24. [DOI: 10.3892/mmr.2017.6791]
  33. Min L, Hong S, Duan H, Zhou Y, Zhang W, Luo Y, et al. Antidifferentiation noncoding RNA regulates the proliferation of osteosarcoma cells. Cancer Biother Radiopharm. 2016;31:52–7. [DOI: 10.1089/cbr.2015.1888]
  34. Han L, Zhang HC, Li L, Li CX, Di X, Qu X. Downregulation of long noncoding RNA HOTAIR and EZH2 induces apoptosis and inhibits proliferation, invasion, and migration of human breast cancer cells. Cancer Biother Radiopharm. 2018;33:241–51. [DOI: 10.1089/cbr.2017.2432]
  35. Zhou X, Ren Y, Kong L, Cai G, Sun S, Song W, et al. Targeting EZH2 regulates tumor growth and apoptosis through modulating mitochondria dependent cell-death pathway in HNSCC. Oncotarget. 2015;6:33720–32. [DOI: 10.18632/oncotarget.5606]
  36. Wang Y, Chen B, Wang Z, Zhang W, Hao K, Chen Y, et al. Marsdenia tenacissimae extraction (MTE) inhibits the proliferation and induces the apoptosis of human acute T cell leukemia cells through inactivating PI3K/AKT/mTOR signaling pathway via PTEN enhancement. Oncotarget. 2016;7:82851–63. [DOI: 10.18632/oncotarget.12654]

MeSH Term

Aged
Apoptosis
Brain Neoplasms
Cell Movement
Cell Proliferation
Enhancer of Zeste Homolog 2 Protein
Female
Glioma
Humans
Male
Middle Aged
PTEN Phosphohydrolase
RNA, Long Noncoding

Chemicals

ANCR long noncoding RNA, human
RNA, Long Noncoding
EZH2 protein, human
Enhancer of Zeste Homolog 2 Protein
PTEN Phosphohydrolase
PTEN protein, human
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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