Type 2 diabetes (T2DM) is a chronic metabolic disease with a high incidence, which seriously affects the physical and mental health of patients. The current treatment methods can only alleviate the disease and are accompanied by unavoidable toxic side effects. Cichorium pumilum Jacq (CG) is a kind of plant medicine with Xinjiang characteristics, which is often used to reduce blood sugar and protect the liver. CG polysaccharide (CGP) is the main active component of CG, but the hypoglycemic effect and mechanism of CGP on T2DM are still unclear. In vitro hypoglycemic and antioxidant experiments showed that CGP had effective hypoglycemic and antioxidant activities, and a series of characterizations of CGP was carried out. In vivo tests on T2DM mice showed that CGP improved liver glycogen metabolism, reduced oxidative stress and colonic damage. AKT and PI3K phosphorylation decreased, mTOR phosphorylation increased in T2DM mice liver; CGP reversed these changes, protected colonic mucosa, and increased Occludin and ZO-1 protein expression. CGP is a good antioxidant and hypoglycemic agent. It improves liver glycogen metabolism and repairs intestinal mucosal damage in T2DM mice via the PI3K/AKT/mTOR pathway, providing a research basis for its treatment.
Background/Aim: Although aldehyde dehydrogenases 1 family member A1 (ALDH1A1) has been extensively studied in cancer, its role in hepatocellular carcinoma (HCC) remains poorly understood. This study was designed to characterize the expression pattern and functional roles of ALDH1A1 in HCC, and to further investigate its underlying molecular mechanisms using integrated proteomic analysis.
Materials and Methods: This study performed a pan-cancer analysis of ALDH1A1 expression, followed by validation of its expression levels in HCC tissue samples and cell lines. The expression of ALDH1A1 was manipulated using small interfering RNAs and lentiviral vector in HCC cell lines. And then the proliferation, migration, invasion, and tumorigenicity of HCC cells were observed in vitro and in vivo. Quantitative proteomic and phosphoproteomic profiling were conducted by liquid chromatography-tandem mass spectrometry, with comprehensive analyses and key findings validated by experiments.
Results: ALDH1A1 was highly expressed in HCC tissues but exhibited notable expression heterogeneity among HCC cell lines. Functionally, ALDH1A1 promoted the proliferation, migration, and tumorigenicity of HCC cells, while suppressing apoptosis and modestly attenuates invasion. Quantitative proteomic and phosphoproteomic analyses revealed that ALDH1A1 profoundly reshaped both protein expression and phosphorylation landscapes in HCC. Furthermore, we validated that ALDH1A1 positively regulates the expression of DMPK, PCMTD2, VAMP4, ARHGAP19, NOL4L, and ST7, while suppressing SLC31A1, DSTYK, CYP4F12, GPNMB expression. Rescue experiments indicated that ALDH1A1 may promote HCC via activating Rho family small GTPase. ALDH1A1 also significantly upregulated mTOR phosphorylation.
Conclusion: ALDH1A1 acts as an oncogenic driver and regulatory hub in HCC.
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