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Int J Biol Sci 2024; 20(5):1744-1762. doi:10.7150/ijbs.86658 This issue Cite

Research Paper

The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma

Zhu Zeng1#, Jie Wang1#, Fengyu Xu1#, Ping Hu1#, Yuhang Hu1, Wenfeng Zhuo1, Ding Chen1, Shengbo Han1, Fan Wang1, Yong Zhao1, Yan Huang1, Gang Zhao1,2✉

1. Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
2. Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
# These authors contributed equally to the paper as first authors.

✉ Corresponding author: Professor Gang Zhao: gangzhaoedu.cn, Phone number: +86-02785726829, Fax: 027-85726935, Address: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefa More

Citation:
Zeng Z, Wang J, Xu F, Hu P, Hu Y, Zhuo W, Chen D, Han S, Wang F, Zhao Y, Huang Y, Zhao G. The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma. Int J Biol Sci 2024; 20(5):1744-1762. doi:10.7150/ijbs.86658. https://www.ijbs.com/v20p1744.htm
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Abstract

Graphic abstract

Glycolysis exerts a key role in the metabolic reprogramming of cancer. Specific long non-coding RNAs (lncRNAs) have been identified to exhibit oncogenic glycolysis regulation. Nevertheless, the precise mechanisms by which glycolysis-related lncRNAs control hepatocellular carcinoma (HCC) are still unknown. We profiled and analyzed glycolysis-associated lncRNA signatures using HCC specimens from The Cancer Genome Atlas (TCGA) dataset. Considerable upregulation of the glycolysis-related lncRNA SLC2A1-DT was noted in HCC tissues; this upregulation was strongly linked with advanced tumor stage and poor prognosis. Cell culture and animal-related studies indicated that knockdown or overexpression of SLC2A1-DT obviously restrained or promoted glycolysis, propagation, and metastasis in HCC cells. Mechanistically, SLC2A1-DT enhanced the interaction of protein between β-catenin and YWHAZ, suppressing the binding between β-catenin and β-TrCP, an E3 ubiquitin ligase. Thereby, SLC2A1-DT impeded the β-TrCP-dependent ubiquitination and β-catenin degradation. The upregulated β-catenin activated the transcription of c-Myc, which then increased the transcription of glycolytic genes including SLC2A1, LDHA, and HK2. Additionally, we revealed that c-Myc transcriptionally induced the expression of methyltransferase 3 (METTL3), which increased N6-methyladenosine (m6A) modification and stability of SLC2A1-DT in a YTHDF1 dependent manner. Collectively, we show that the lncRNA SLC2A1-DT promotes glycolysis and HCC tumorigenesis by a m6A modification-mediated positive feedback mechanism with glycolytic regulator c-Myc and suggested as an innovative treatment option and indicator for HCC.

Keywords: Hepatocellular carcinoma, m6A modification, SLC2A1-DT, β-catenin, c-Myc, Glycolysis.

Citation styles

APA
Zeng, Z., Wang, J., Xu, F., Hu, P., Hu, Y., Zhuo, W., Chen, D., Han, S., Wang, F., Zhao, Y., Huang, Y., Zhao, G. (2024). The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma. International Journal of Biological Sciences, 20(5), 1744-1762. https://doi.org/10.7150/ijbs.86658.

ACS
Zeng, Z.; Wang, J.; Xu, F.; Hu, P.; Hu, Y.; Zhuo, W.; Chen, D.; Han, S.; Wang, F.; Zhao, Y.; Huang, Y.; Zhao, G. The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma. Int. J. Biol. Sci. 2024, 20 (5), 1744-1762. DOI: 10.7150/ijbs.86658.

NLM
Zeng Z, Wang J, Xu F, Hu P, Hu Y, Zhuo W, Chen D, Han S, Wang F, Zhao Y, Huang Y, Zhao G. The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma. Int J Biol Sci 2024; 20(5):1744-1762. doi:10.7150/ijbs.86658. https://www.ijbs.com/v20p1744.htm

CSE
Zeng Z, Wang J, Xu F, Hu P, Hu Y, Zhuo W, Chen D, Han S, Wang F, Zhao Y, Huang Y, Zhao G. 2024. The m6A modification-mediated positive feedback between glycolytic lncRNA SLC2A1-DT and c-Myc promotes tumorigenesis of hepatocellular carcinoma. Int J Biol Sci. 20(5):1744-1762.

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