PYCR1 Downregulation Induces Autophagy Dependent Apoptosis Through Inhibiting PI3K/AKT/mTOR Axis in Human Hepatocellular Carcinoma Cells

Background: Hepatocellular carcinoma (HCC) is a global malignant tumor type. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a metabolic enzyme that exhibits pro-tumor properties in Cancer progression. However, the exact molecular mechanism of PYCR1 in HCC progression is still unclear.

Methods: CCK8, EdU, and Transwell assays were used to measure the proliferation, migration, and invasion of HCC cells, respectively. Immunostaining and flow cytometry were used to detect cellular Autophagy and Apoptosis.

Results: The downregulation of PYCR1 can inhibit the survival, proliferation, migration, and invasion of HCC cells. At the same time, downregulation of PYCR1 induces Autophagy and subsequently activates cell Apoptosis. Therefore, we pretreated HCC cells with mTOR activators or inhibitors to inhibit or promote Autophagy, leading to an inhibition or an increase in Apoptosis. Simultaneously, the PI3K activators or inhibitors to activate or inhibit the PI3K/Akt/mTOR pathway also lead to inhibition or activation of Autophagy and Apoptosis.

Conclusion: The downregulation of PYCR1 induces autophagy-dependent Apoptosis in HCC cells by inhibiting the PI3K/Akt/mTOR pathway, revealing a novel mechanistic link in HCC pathophysiology.

apoptosis; autophagy; hepatocellular carcinoma; pyrroline-5-carboxylate reductase 1.