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

Cancer Gene Therapy volume 28, pages 1025–1034 (2021)Cite this article

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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.

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Fig. 1: ANCR and EZH2 are highly expressed, and PTEN is poorly expressed in human glioma tissues.
Fig. 2: ANCR and EZH2 are highly expressed while PTEN is poorly expressed in human glioma cells.
Fig. 3: LncRNA ANCR directly interacted with EZH2/ PTEN in glioma cells.
Fig. 4: Repressed ANCR and silenced EZH2 restrain invasion, migration, and viability of human glioma cells while inducing apoptosis.
Fig. 5: Elevation of PTEN restricts malignant behaviors of human glioma cells.

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Acknowledgements

We acknowledge the reviewers for their helpful comments on this paper.

Funding

This work was supported by Youth Projects Natural Science Foundation of Anhui Province (1508085QHl84); Joint Research Projects for Public Welfare in Anhui Province (15011d04033); Fundamental Research Fund for Central Universities (WK 9110000032).

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Authors and Affiliations

  1. High Magnetic Field Laboratory, Chinese Academy of Sciences, Mailbox 1110, 350 Shushanhu Road, Hefei, Anhui, 230031, P. R. China

    Chuandong Cheng

  2. University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China

    Chuandong Cheng

  3. 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

    Chuandong Cheng, Yongfei Dong, Xiaoyu Ru, Yanghua Xia & Ying Ji

  4. Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei, Anhui, 230036, P. R. China

    Chuandong Cheng, Yongfei Dong, Xiaoyu Ru, Yanghua Xia & Ying Ji

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Correspondence to Yanghua Xia or Ying Ji.

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Cheng, C., Dong, Y., Ru, X. et al. LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression. Cancer Gene Ther 28, 1025–1034 (2021). https://doi.org/10.1038/s41417-020-00263-8

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