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.
Keyphrases
- poor prognosis
- cell death
- cell proliferation
- single cell
- long non coding rna
- end stage renal disease
- oxidative stress
- signaling pathway
- fluorescent probe
- dna damage
- chronic kidney disease
- newly diagnosed
- living cells
- genome wide
- endoplasmic reticulum stress
- clinical trial
- gene expression
- ejection fraction
- reactive oxygen species
- rna seq
- stem cells
- peritoneal dialysis
- bone marrow
- risk assessment
- binding protein
- drug delivery
- pi k akt
- human health
- high glucose