The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma.
Zhe LiJiwei ZhangXinyang LiuShengli LiQifeng Wangnull Di ChenZhixiang HuTao YuJie DingJinjun LiMing YaoJia FanShengling HuangQiang GaoYingjun ZhaoXiang-Huo HePublished in: Nature communications (2018)
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.
Keyphrases
- cell proliferation
- long non coding rna
- long noncoding rna
- pi k akt
- small molecule
- cell cycle
- nitric oxide
- end stage renal disease
- binding protein
- transcription factor
- newly diagnosed
- type diabetes
- single molecule
- adipose tissue
- rna seq
- cell migration
- insulin resistance
- single cell
- metabolic syndrome
- circulating tumor
- smoking cessation