Fig. 5: ALDH7A1 knockdown inhibits glycolysis of heat-induced HCC cells and sensitizes the cells to hyperosmotic stress. | Cell Death Discovery

Fig. 5: ALDH7A1 knockdown inhibits glycolysis of heat-induced HCC cells and sensitizes the cells to hyperosmotic stress.

From: Tanshinone IIA inhibits heat-induced growth of p53-mutant Huh-7 hepatocellular carcinoma by modulating osmotic homeostasis and glycolysis through targeting ALDH7A1

Fig. 5

A ALDH7A1 is overexpressed at mRNA level in HCC tissues, compared with normal liver tissue (analyzed using GEPIA2). B, C Validation of the reduced expression of ALDH7A1 at mRNA and protein level after shRNA lentiviral infection using qPCR and western blotting. D–F Knockdown of ALDH7A1 inhibits glucose uptake, lactate production, and ATP production. G–O Seahorse analyses of OCR and ECAR: the cells with low level of ALDH7A1 have significantly decreased OCR and ECAR values. P, Q ALDH7A1 knockdown reduces its downstream osmolytic and enzymatic products betaine and d-glycerate. ALDH7A1 knockdown does not influence NADH (R) or LPO (S), but reduces ROS (T). For (A–T), *p < 0.05, **p < 0.01, compared with shNC; NS not significant. U ALDH7A1 knockdown inhibits the viability (at 72 h) of heat-induced Huh-7 cells in isosmotic or hyperosmotic conditions. Iso isosmotic, Hyper Hyperosmotic. V–X ALDH7A1 knockdown increases the sensitivity of heat-induced HCC cells to hyperosmotic stress: knockdown of ALDH7A1 results in more apoptotic cells and less invasive cell in NaCl- or glucose-mediated hyperosmotic conditions. Y–Z ALDH7A1 knockdown reduces MMP2, MMP9, and N-cadherin in isosmotic media, and only reduces MMP2 and MMP9 in NaCl-mediated hyperosmotic media. For U–Z, **p < 0.01, compared with shNC+Iso group; ## p < 0.01, compared with shALDH7A1+Iso group; ++ p < 0.01, compared with shNC+Hyper/NaCl or shNC+Hyper/Glucose group; NS not significant.

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