2. Academic Validation
  3. The cancer-testis lncRNA LINC01977 promotes HCC progression by interacting with RBM39 to prevent Notch2 ubiquitination

The cancer-testis lncRNA LINC01977 promotes HCC progression by interacting with RBM39 to prevent Notch2 ubiquitination

  • Cell Death Discov. 2023 May 18;9(1):169. doi: 10.1038/s41420-023-01459-1.
Anliang Xia # 1,  Qi Yue # 2,  Mingming Zhu # 1,  Jianbo Xu # 3,  Siyuan Liu 1,  Yue Wu 1,  Zhangding Wang 4,  Zhu Xu 1,  Hongda An 1,  Qiang Wang 5,  Shouyu Wang 6 7,  Beicheng Sun 8 9
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
  • 2 Nanjing Drum Tower Hospital, Clinical College of Jiangsu University, Nanjing, China.
  • 3 Department of Hepatobiliary Surgery, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
  • 4 Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 5 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China. njmuwangqiang@163.com.
  • 6 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. sywang@nju.edu.cn.
  • 7 Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China. sywang@nju.edu.cn.
  • 8 Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. sunbc@nju.edu.cn.
  • 9 Nanjing Drum Tower Hospital, Clinical College of Jiangsu University, Nanjing, China. sunbc@nju.edu.cn.
  • # Contributed equally.
PMID: 37198207 DOI: 10.1038/s41420-023-01459-1
Abstract

Cancer-testis genes are involved in the occurrence and development of Cancer, but the role of cancer-testis-associated lncRNAs (CT-lncRNAs) in hepatocellular carcinoma (HCC) remains to be explored. Here, we discovered a novel CT-lncRNA, LINC01977, based on the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. LINC01977 was exclusively expressed in testes and highly expressed in HCC. High LINC01977 levels correlated with poorer overall survival (OS) in individuals with HCC. Functional assays showed that LINC01977 promoted HCC growth and metastasis in vitro and in vivo. Mechanistically, LINC01977 directly bound to RBM39 to promote the further entry of Notch2 into the nucleus, thereby preventing the ubiquitination and degradation of Notch2. Furthermore, the RNA binding protein IGF2BP2, one of the m6A modification readers, enhanced the stability of LINC01977, resulting in its high level in HCC. Therefore, the data suggest that LINC01977 interacts with RBM39 and promotes the progression of HCC by inhibiting Notch2 ubiquitination and degradation, indicating that LINC01977 may be a potential biomarker and therapeutic target for HCC patients.

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