ABSTRACT
Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Kinesins/metabolism , Aged , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Janus Kinases/metabolism , Kinesins/genetics , Male , Middle Aged , Prognosis , STAT3 Transcription Factor/metabolism , Signal TransductionABSTRACT
Reactive oxygen species (ROS) have been associated with acute ethanol-induced liver damage. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct antioxidant. In this study, we investigated the effects of NAC on acute ethanol-induced liver damage. Female ICR mice were administered by gavage with a single dose of ethanol (6g/kg). NAC was administered in two different modes. In mode A, mice were injected with different doses of NAC at 30min before ethanol. In mode B, mice were injected with different doses of NAC at 4h after ethanol. Acute ethanol-induced liver damage was estimated by measuring serum alanine aminotransferase (ALT) activity and histopathological changes. Result showed that a single dose of ethanol (6g/kg) caused a significant increase in serum ALT activity, followed by microvesicular steatosis and necrosis in mouse liver. Pretreatment with NAC significantly protected against acute ethanol-induced liver damage in a dose-independent manner. Correspondingly, pretreatment with NAC significantly attenuated acute ethanol-induced lipid peroxidation and GSH depletion and inhibited hepatic TNF-alpha mRNA expression. By contrast, post-treatment with NAC aggravated ethanol-induced hepatic lipid peroxidation and worsened acute ethanol-induced liver damage in a dose-dependent manner. Taken together, NAC has a dual effect on acute ethanol-induced liver damage. Pretreatment with NAC prevent from acute ethanol-induced liver damage via counteracting ethanol-induced oxidative stress. When administered after ethanol, NAC might behave as a pro-oxidant and aggravate acute ethanol-induced liver damage.
