PADI3 induces cell cycle arrest via the Sirt2/AKT/p21 pathway and acts as a tumor suppressor gene in colon cancer

Objective:As a member of the peptidyl arginine deiminase(PAD)family,PADI3 is weakly expressed in colon cancer tissues and highly expressed in adjacent colon cancer tissues.However,the role of PADI3 in colon cancer is unclear.In this study,we investigated the function and molecular mechanism of PADI3 in colon cancer tumorigenesis.Methods:Western blot and real-time PCR were used to detect the expression levels of several genes.CCK-8,flow cytometry(FCM)and colony formation assays were used to examine cell proliferation,the cell cycle and colony formation ability.RNAsequencing analysis was used to study the molecular mechanism of PADI3 in tumorigenesis.A truncation mutation experiment was performed to determine the key functional domain of PADI3.Results:PADI3 overexpression inhibited cell proliferation and colony formation and led to G1 phase arrest in both HCT116(originating from primary colon cancer)and LoVo(originating from metastatic tumor nodules of colon cancer)cells.PADI3-expressing HCT116 cells had a lower tumor formation rate and produced smaller tumors than control cells.PADI3 significantly decreased Sirtuin2(Sirt2)and Snail expression and AKT phosphorylation and increased p21 expression,and Sirt2 overexpression partly reversed the effects induced by PADI3 overexpression.Immunocytochemistry showed that PADI3 is mainly localized in the cytoplasm.Truncation mutation experiments showed that the C-domain is the key domain involved in the antitumor activity of PADI3.Conclusions:PADI3 suppresses Snail expression and AKT phosphorylation and promotes p21 expression by downregulating Sirt2 expression in the cytoplasm,and the C-domain is the key domain for its antitumor activity.

Research advances on antioxidation,neuroprotection,and molecular mechanisms of Lycium barbarum polysaccharides

Lycium barbarum polysaccharides(LBPs)are the major polysaccharides extracted from L.barbarum,which is used in traditional Chinese medicine(TCM)for treating diseases.Studies have shown that LBPs have important biological activities,such as antioxidation,anti-aging,neuroprotection,immune regulation.LBPs inhibit oxidative stress,improve neurodegeneration and stroke-induced neural injury,increase proliferation and differentiation of neural stem cell,and promote neural regeneration.Here we have reviewed latest advances in the biomedical activities of LBPs and improved methods for the isolation,extraction,and purification of LBPs.Then,new discoveries to decrease oxidative stress and cellular apoptosis,inhibit aging progress,and improve neural repair in neurodegeneration and ischemic brain injury have been discussed in detail through in vitro cell culture and in vivo animal studies.Importantly,the molecular mechanisms of LBPs in playing neuroprotective roles are further explored.Lastly,we discuss the perspective of LBPs as biomedical compounds in TCM and modern medicine and provide the experimental and theoretical evidence to use LBPs for the treatment of aging-related neurological diseases and stroke-induced neural injuries.