Cystathionine‐γ‐Lyase/Hydrogen Sulfide Axis Plays a Crucial Role in Promoting the Progression of Cervical Cancer

ABSTRACT

The role of endogenous hydrogen sulfide (H ₂ S) in the pathophysiological mechanisms of various organ tumors has been extensively studied; however, its relevance to cervical cancer remains unexplored. This study aimed to examine the effect of endogenous H ₂ S and its main synthetic enzyme, cystathionine‐γ‐lyase (CSE), in regulating the growth behavior in cervical cancer cells. The proliferation, migration, and invasion of C33A and HeLa cervical cancer cells were investigated, followed by molecular, biochemical, and immunocytochemical analyses. The results indicated that CSE is highly expressed in C33A and HeLa cells and modulates the levels of endogenous H ₂ S. CSE knockdown suppressed the proliferation, migration, and invasion of cervical cancer cells. The CSE‐mediated growth patterns involved epithelial–mesenchymal transition (EMT), mitochondrial apoptosis, pyroptosis, reactive oxygen species (ROS) production, and the PI3K/AKT/mTOR signaling pathway. Additionally, CSE knockdown inhibited the growth of xenograft tumors in vivo. Similarly, CSE overexpression was performed for reverse verification. In brief, inhibition of CSE reduced cervical cancer growth, while overexpression of CSE promoted it. These findings indicated that CSE may serve as a potential target for early diagnosis, prognosis assessment, and therapeutic intervention in cervical cancer.