2. Academic Validation
  3. METTL3/YTHDC1-mediated upregulation of LINC00294 promotes hepatocellular carcinoma progression

METTL3/YTHDC1-mediated upregulation of LINC00294 promotes hepatocellular carcinoma progression

  • Heliyon. 2023 Nov 23;9(12):e22595. doi: 10.1016/j.heliyon.2023.e22595.
Rulin Zhang 1,  Rui Yang 1 2 3,  Zhuodeng Huang 1 2 3,  Xiang Xu 1 2 3,  Siang Lv 1 2 3,  Xin Guan 1,  Hao Li 4 5,  Jun Wu 1 2 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201803, China.
  • 2 Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China.
  • 3 The Key Laboratory of Molecular Pathology (Hepatobiliary Diseases) of Guangxi, Baise 533000, China.
  • 4 Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361005, Fujian, China.
  • 5 Department of Pancreatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
PMID: 38125436 DOI: 10.1016/j.heliyon.2023.e22595
Abstract

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy and the third highest contributor to cancer-associated deaths globally. Research has increasingly demonstrated a strong correlation between long noncoding RNAs (lncRNAs) and the incidence and progression of HCC. Nonetheless, the exact mechanism whereby the function of lncRNAs in HCC has not been elucidated. This study explored the pathological role of LINC00294 in HCC, as well as the modulatory mechanism involved. Based on the "The Cancer Genome Atlas (TCGA)" database and validation in HCC cell lines and tissues, the expression of LINC00294 was discovered to be upregulated in HCC tissues and correlated with tumor grade and the prognosis of patients with HCC. Functionally, LINC00294 stimulated the proliferation of HCC cells as well as the Warburg effect (aerobic glycolysis) to enhance progression of tumor in vivo. Mechanistically, METTL3/YTHDC1-mediated N6-methyladenosine (m6A) modification underwent a significant enrichment within LINC00294 and was shown to enhance its RNA stability. Moreover, LINC00294 promoted the interaction between YTHDC1 and HK2 and GLUT1 mRNA. Overall, our study illustrates the m6A modification-mediated epigenetic mechanism of LINC00294 expression and regulatory role in HK2and GLUT1 mRNA expression and indicate LINC00294 as a potential biomarker panel for prognostic prediction and treatment in HCC.

Keywords

Hepatocellular carcinoma; LINC00294; METTL3; N6-methyladenosine modification; YTHDC1.

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