Int J Biol Sci 2023; 19(2):362-376. doi:10.7150/ijbs.69784 This issue Cite

Research Paper

FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway

Dong Ma1,2*, Pengpeng Liu1,3*, Junjun Wen1*, Yang Gu4, Zhangshuo Yang1, Jianwei Lan1,3, Haining Fan2✉, Zhisu Liu1✉, Deliang Guo1✉

1. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, P.R. China.
2. Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qinghai University, Xining, 810000, P.R. China.
3. Department of Hepatobiliary Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, P.R. China.
4. Department of Hepatobiliary and Pancreas, The First People's Hospital of Jingmen, Jingmen, 448000, P.R. China.
*These authors contributed equally to this work.

Citation:
Ma D, Liu P, Wen J, Gu Y, Yang Z, Lan J, Fan H, Liu Z, Guo D. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. Int J Biol Sci 2023; 19(2):362-376. doi:10.7150/ijbs.69784. https://www.ijbs.com/v19p0362.htm
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Abstract

Graphic abstract

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer deaths globally. Although considerable progress has been made in the treatment, clinical outcomes of HCC patients are still poor. Therefore, it is necessary to find novel prognostic factors upon which prevention and treatment strategies can be formulated. Ficolin-3 (FCN3) protein is a member of the human ficolin family. It activates complement through pathways associated with mannose-binding lectin-associated serine proteases. Herein, we identified that FCN3 was downregulated in HCC tissues and decreased FCN3 expression was closely related to poor prognosis. Overexpression of FCN3 induced apoptosis and inhibited cell proliferation via the p53 signaling pathway. Mechanistically, FCN3 modulated the nuclear translocation of eukaryotic initiation factor 6 (EIF6) by binding ribosome maturation factor (SBDS), which induced ribosomal stress and activation of the p53 pathway. In addition, Y-Box Binding Protein 1 (YBX1) involved in the transcription and translation level regulation of FCN3 to SBDS. Besides, a negative feedback loop in the downstream of FCN3 involving p53, YBX1 and SBDS was identified.

Keywords: Hepatocellular carcinoma, FCN3, SBDS, p53 signaling pathway, Ribosomal stress


Citation styles

APA
Ma, D., Liu, P., Wen, J., Gu, Y., Yang, Z., Lan, J., Fan, H., Liu, Z., Guo, D. (2023). FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. International Journal of Biological Sciences, 19(2), 362-376. https://doi.org/10.7150/ijbs.69784.

ACS
Ma, D.; Liu, P.; Wen, J.; Gu, Y.; Yang, Z.; Lan, J.; Fan, H.; Liu, Z.; Guo, D. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. Int. J. Biol. Sci. 2023, 19 (2), 362-376. DOI: 10.7150/ijbs.69784.

NLM
Ma D, Liu P, Wen J, Gu Y, Yang Z, Lan J, Fan H, Liu Z, Guo D. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. Int J Biol Sci 2023; 19(2):362-376. doi:10.7150/ijbs.69784. https://www.ijbs.com/v19p0362.htm

CSE
Ma D, Liu P, Wen J, Gu Y, Yang Z, Lan J, Fan H, Liu Z, Guo D. 2023. FCN3 inhibits the progression of hepatocellular carcinoma by suppressing SBDS-mediated blockade of the p53 pathway. Int J Biol Sci. 19(2):362-376.

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