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

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 1572 (04 20 2018) ISSN: 2041-1723 [Electronic] England
• PMID: 29679004 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Long Noncoding
• PRMT5 protein, human
• Protein-Arginine N-Methyltransferases
• Proteasome Endopeptidase Complex

Topics

• Animals
• CRISPR-Cas Systems (genetics)
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• HEK293 Cells
• Humans
• Liver Neoplasms (genetics, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Invasiveness (genetics)
• Neoplasm Transplantation
• Oncogenes (genetics)
• Prognosis
• Proteasome Endopeptidase Complex (metabolism)
• Protein-Arginine N-Methyltransferases (metabolism)
• RNA, Long Noncoding (genetics)
• Transplantation, Heterologous