2. Academic Validation
  3. Non-coding small nucleolar RNA SNORD17 promotes the progression of hepatocellular carcinoma through a positive feedback loop upon p53 inactivation

Non-coding small nucleolar RNA SNORD17 promotes the progression of hepatocellular carcinoma through a positive feedback loop upon p53 inactivation

  • Cell Death Differ. 2022 May;29(5):988-1003. doi: 10.1038/s41418-022-00929-w.
Junnan Liang  # 1 2 3,  Ganxun Li  # 1 2 3,  Jingyu Liao  # 1 2 3,  Zhao Huang  # 1 2 3,  Jingyuan Wen 1 2 3,  Yu Wang 1 2 3,  Zeyu Chen 1 2 3,  Guangzhen Cai 1 2 3,  Weiqi Xu 1 2 3,  Zeyang Ding 1 2 3,  Huifang Liang 1 2 3,  Pran K Datta 4,  Liang Chu 5 6 7,  Xiaoping Chen 8 9 10 11,  Bixiang Zhang 12 13 14 15
Affiliations

Affiliations

  • 1 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China.
  • 3 Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Division of Hematology and Oncology, Department of Medicine, UAB Comprehensive Cancer Center, Birmingham, AL, USA.
  • 5 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 6 Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China. [email protected].
  • 7 Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 8 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 9 Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China. [email protected].
  • 10 Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 11 Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China. [email protected].
  • 12 Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 13 Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Wuhan, China. [email protected].
  • 14 Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
  • 15 Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China. [email protected].
  • # Contributed equally.
PMID: 35034103 DOI: 10.1038/s41418-022-00929-w
Abstract

Recent evidence suggests that small nucleolar RNAs (snoRNAs) are involved in the progression of various cancers, but their precise roles in hepatocellular carcinoma (HCC) remain largely unclear. Here, we report that SNORD17 promotes the progression of HCC through a positive feedback loop with p53. HCC-related microarray datasets from the Gene Expression Omnibus (GEO) database and clinical HCC samples were used to identify clinically relevant snoRNAs in HCC. SNORD17 was found upregulated in HCC tissues compared with normal liver tissues, and the higher expression of SNORD17 predicted poor outcomes in patients with HCC, especially in those with wild-type p53. SNORD17 promoted the growth and tumorigenicity of HCC cells in vitro and in vivo by inhibiting p53-mediated cell cycle arrest and Apoptosis. Mechanistically, SNORD17 anchored nucleophosmin 1 (NPM1) and MYB binding protein 1a (MYBBP1A) in the nucleolus by binding them simultaneously. Loss of SNORD17 promoted the translocation of NPM1 and MYBBP1A into the nucleoplasm, leading to NPM1/MDM2-mediated stability and MYBBP1A/p300-mediated activation of p53. Interestingly, p300-mediated acetylation of p53 inhibited SNORD17 expression by binding to the promoter of SNORD17 in turn, forming a positive feedback loop between SNORD17 and p53. Administration of SNORD17 Antisense Oligonucleotides (ASOs) significantly suppressed the growth of xenograft tumors in mice. In summary, this study suggests that SNORD17 drives Cancer progression by constitutively inhibiting p53 signaling in HCC and may represent a potential therapeutic target for HCC.

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