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The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma

Author

Listed:
  • Zhe Li

    (Shanghai Medical College, Fudan University)

  • Jiwei Zhang

    (Shanghai Medical College, Fudan University)

  • Xinyang Liu

    (Shanghai Medical College, Fudan University)

  • Shengli Li

    (Shanghai Medical College, Fudan University)

  • Qifeng Wang

    (Shanghai Medical College, Fudan University)

  • Di Chen

    (Shanghai Medical College, Fudan University)

  • Zhixiang Hu

    (Shanghai Medical College, Fudan University)

  • Tao Yu

    (Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jie Ding

    (Shanghai Medical College, Fudan University)

  • Jinjun Li

    (Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine)

  • Ming Yao

    (Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jia Fan

    (Shanghai Medical College, Fudan University)

  • Shenglin Huang

    (Shanghai Medical College, Fudan University)

  • Qiang Gao

    (Shanghai Medical College, Fudan University)

  • Yingjun Zhao

    (Shanghai Medical College, Fudan University)

  • Xianghuo He

    (Shanghai Medical College, Fudan University
    Shanghai Medical College, Fudan University)

Abstract

Recurrent chromosomal aberrations have led to the discovery of oncogenes or tumour suppressors involved in carcinogenesis. Here we characterized an oncogenic long intergenic non-coding RNA in the frequent DNA-gain regions in hepatocellular carcinoma (HCC), LINC01138 (long intergenic non-coding RNA located on 1q21.2). The LINC01138 locus is frequently amplified in HCC; the LINC01138 transcript is stabilized by insulin like growth factor-2 mRNA-binding proteins 1/3 (IGF2BP1/IGF2BP3) and is associated with the malignant features and poor outcomes of HCC patients. LINC01138 acts as an oncogenic driver that promotes cell proliferation, tumorigenicity, tumour invasion and metastasis by physically interacting with arginine methyltransferase 5 (PRMT5) and enhancing its protein stability by blocking ubiquitin/proteasome-dependent degradation in HCC. The discovery of LINC01138, a promising prognostic indicator, provides insight into the molecular pathogenesis of HCC, and the LINC01138/PRMT5 axis is an ideal therapeutic target for HCC treatment.

Suggested Citation

  • Zhe Li & Jiwei Zhang & Xinyang Liu & Shengli Li & Qifeng Wang & Di Chen & Zhixiang Hu & Tao Yu & Jie Ding & Jinjun Li & Ming Yao & Jia Fan & Shenglin Huang & Qiang Gao & Yingjun Zhao & Xianghuo He, 2018. "The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04006-0
    DOI: 10.1038/s41467-018-04006-0
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