Sulfiredoxin-1 promotes the growth of hepatocellular carcinoma by inhibiting TFEB-mediated autophagy and lysosome biogenesis.
Exp Cell Res
; 441(2): 114169, 2024 Aug 15.
Article
in En
| MEDLINE
| ID: mdl-39029574
ABSTRACT
Advanced hepatocellular carcinoma (HCC) patients have poor prognosis. As an endogenous antioxidant enzyme involved in a variety of bioprocesses, sulfiredoxin-1 (SRXN1) plays an irreplaceable role in promoting the development of tumors. However, the role and working mechanism of SRXN1 in HCC remain unclear. In this study, we confirmed that SRXN1 promoted the cell proliferation of HCC at genetic and pharmacological level, respectively. Transcriptome sequencing analysis revealed SRXN1 knockdown had a significant effect on the expression of lysosome biogenesis related genes. Further experiments validated that lysosome biogenesis and autophagic flux were enhanced after SRXN1 inhibition and reduced as SRXN1 overexpression. Mechanism study revealed that ROS accumulation induced TFEB nuclear translocation, followed by increased autophagy. Following this rationale, the combination of SRXN1 inhibitor and sorafenib demonstrated noticeable synergistic antitumor effect through the boost of ROS both in vivo and in vitro. Taken together, SRXN1 could be a potential therapeutic target for HCC therapy.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autophagy
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Carcinoma, Hepatocellular
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Cell Proliferation
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Oxidoreductases Acting on Sulfur Group Donors
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Liver Neoplasms
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Lysosomes
Limits:
Animals
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Humans
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Male
Language:
En
Year:
2024
Type:
Article