2. Academic Validation
  3. m6A methylation-mediated lncRNA RNF144A-AS1 promotes hepatocellular carcinoma progression through the miR-1301-3p/RNF38 pathway

m6A methylation-mediated lncRNA RNF144A-AS1 promotes hepatocellular carcinoma progression through the miR-1301-3p/RNF38 pathway

  • Biol Direct. 2025 Jul 29;20(1):91. doi: 10.1186/s13062-025-00681-4.
Minyu Kong # 1 2,  Wendong Li # 1 2,  Hao Li # 1 2,  Yifan Jing 3,  Min Xu 1 2,  Yuting He 4 5,  Wenzhi Guo 6 7
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 2 Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. fccheyt1@zzu.edu.cn.
  • 5 Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. fccheyt1@zzu.edu.cn.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. fccguowz@zzu.edu.cn.
  • 7 Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. fccguowz@zzu.edu.cn.
  • # Contributed equally.
PMID: 40734179 DOI: 10.1186/s13062-025-00681-4
Abstract

Background: Globally, HCC is still one of the most common cancers. N6-methyladenosine (m6A) modifications and long-stranded noncoding RNAs (lncRNAs) play key roles in regulating HCC progression. The role of the lncRNA RNF144A-AS1, a newly identified lncRNA, in HCC is unclear.

Methods: In HCC, RNF144A-AS1 expression level and its effect on prognosis were investigated by bioinformatics. CCK-8, EdU, scratch assay, and Transwell assays were used to detect the impact of RNF144A-AS1 on hepatocellular carcinoma malignancy. Assays using MeRIP-qPCR, RIP, and Actinomycin D were used to study the effects of m6A methylation on hepatocellular carcinoma malignant phenotypes. Revealing the potential mechanism of action of RNF144A-AS1 by luciferase reporter gene assay, PCR, and Western blot assays, and Nude mice subcutaneous load cell and lung metastasis models were used to verify the effect of RNF144A-AS1 on the malignant phenotype of tumors in vivo.

Results: The lncRNA RNF144A-AS1 was significantly upregulated in HCC, and it was significantly associated with poor prognosis. Functionally, HCC cells with RNF144A-AS1 knockdown were inhibited in terms of proliferation, migration, and invasion. Further studies in vivo confirmed that RNF144A-AS1 knockdown inhibited tumor cell growth and metastasis. Mechanistically, METTL3 increased the m6A modification and stability of RNF144A-AS1 in an IGF2BP1-associated manner. In addition, RNF144A-AS1 was inhibited by sponge-like miR-1301-3p to inhibit RNF38 degradation, thereby promoting the HCC malignant phenotype.

Conclusion: The RNF144A-AS1 gene is affected by METTL3/IGF2BP1 methylation and encourages liver Cancer proliferation and metastasis by increasing expression of RNF38 through sponge-like miR-1301-3p. RNF144-AS1 promises to be a therapeutic target for HCC.

Keywords

HCC; biomarker; lncRNA.

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