2. Academic Validation
  3. LINC00470 Coordinates the Epigenetic Regulation of ELFN2 to Distract GBM Cell Autophagy

LINC00470 Coordinates the Epigenetic Regulation of ELFN2 to Distract GBM Cell Autophagy

  • Mol Ther. 2018 Sep 5;26(9):2267-2281. doi: 10.1016/j.ymthe.2018.06.019.
Changhong Liu 1,  Haijuan Fu 1,  Xiaoping Liu 2,  Qianqian Lei 3,  Yan Zhang 4,  Xiaoling She 5,  Qiang Liu 6,  Qing Liu 7,  Yingnan Sun 8,  Guiyuan Li 1,  Minghua Wu 9
Affiliations

Affiliations

  • 1 Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis, Ministry of Health, Changsha 410078, Hunan, China.
  • 2 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
  • 3 Department of Pathology, Zhengzhou University People's Hospital & Henan Provincial People's Hospital, Zhengzhou 450000, Henan, China.
  • 4 Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis, Ministry of Health, Changsha 410078, Hunan, China.
  • 5 Second Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
  • 6 Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
  • 7 Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
  • 8 Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
  • 9 Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha 410078, Hunan, China; Key Laboratory of Carcinogenesis, Ministry of Health, Changsha 410078, Hunan, China. Electronic address: [email protected].
PMID: 30037656 DOI: 10.1016/j.ymthe.2018.06.019
Abstract

The Epigenetics and genomics of glioblastoma (GBM) are complicated. Previous reports indicate that ELFN2 is widely distributed in the cerebral cortex neurons, striatum, and hippocampus cone and in granular cells. However, the function and mechanism of ELFN2, particularly in GBM, have rarely been explored. In this study, we identified ELFN2 as a new hypomethylation gene that acts as an oncogene in GBM. ELFN2 promoted cell Autophagy by interacting with AurkA and eIF2α and inhibiting the activation of AurkA. We also demonstrated that aberrantly high ELFN2 expression is obtained due to hypomethylation of its promoter and abnormal miR-101 and LINC00470 expression in GBM. LINC00470 not only enhanced the expression of ELFN2 through adsorption of miR-101 but also affected the methylation level of ELFN2 by decreasing H3K27me3 occupancy. In addition, LINC00470 played a dominant role in the regulation of GBM cell Autophagy, even though it upregulated ELFN2 expression. The results indicate that the combination of LINC00470 and ELFN2 has important significance for evaluating the prognosis of astrocytoma patients.

Keywords

AurkA; cell autophagy; long noncoding RNA; methylation modification; miR-101.

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