The cancer-testis lncRNA lnc-CTHCC promotes hepatocellular carcinogenesis by binding hnRNP K and activating YAP1 transcription.
Anliang XiaWenwen YuanQiang WangJianbo XuYayun GuLiansheng ZhangChen ChenZhangding WangDi WuQifeng HeWeiwei YuFei WangCailin XueYan ZhangGuojian BaoXuewen TaoSiyuan LiuShouyu WangZhi-Bin HuBeicheng SunPublished in: Nature cancer (2022)
Cancer-testis (CT) genes participate in the initiation and progression of cancer, but the role of CT-associated long non-coding RNAs (CT-lncRNAs) in hepatocellular carcinoma (HCC) is still elusive. Here, we discovered a conserved CT-lncRNA, named lnc-CTHCC, which was highly expressed in the testes and HCC. A lnc-CTHCC-knockout (KO) mouse model further confirmed that the global loss of lnc-CTHCC inhibited the occurrence and development of HCC. In vitro and in vivo assays also showed that lnc-CTHCC promoted HCC growth and metastasis. Mechanistically, lnc-CTHCC bound to heterogeneous nuclear ribonucleoprotein K (hnRNP K), which was recruited to the YAP1 promoter for its activation. Additionally, the N 6 -methyladenosine (m 6 A) modification was mediated by N 6 -adenosine-methyltransferase 70-kDa subunit (METTL3) and recognized by insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)/IGF2BP3, which maintained lnc-CTHCC stability and increased its expression in HCC. Together, our results show that lnc-CTHCC directly binds to hnRNP K and promotes hepatocellular carcinogenesis and progression by activating YAP1 transcription, suggesting that lnc-CTHCC is a potential biomarker and therapeutic target of HCC.
Keyphrases
- binding protein
- long non coding rna
- papillary thyroid
- computed tomography
- image quality
- poor prognosis
- transcription factor
- dual energy
- contrast enhanced
- mouse model
- signaling pathway
- magnetic resonance imaging
- dna methylation
- positron emission tomography
- gene expression
- magnetic resonance
- pi k akt
- squamous cell carcinoma
- high throughput
- lymph node metastasis
- heat shock protein
- genome wide
- protein kinase
- childhood cancer