ABSTRACT
Hepatocellular carcinoma (HCC) occurs mainly in patients with chronic liver disease and cirrhosis. Increasing evidence has identified the involvement of microRNAs (miRNAs) acting as essential regulators in the progression of HCC. As predicted by microarray analysis, miR-448 might potentially affect HCC progression by regulating the melanoma-associated antigen (MAGEA). Therefore, the present investigation focused on exploring whether or not miR-448 and MAGEA6 were involved in the self-renewal and stemness maintenance of HCC stem cells. The interaction among miR-448, MAGEA6, and the AMPK signaling pathway was evaluated. It was noted that miR-448 targeted and downregulated MAGEA6, thus activating the AMP-activated protein kinase (AMPK) signaling pathway in HCC. Furthermore, for the purpose of exploring the functional relevance of MAGEA6 and miR-448 on the sphere formation, colony formation, and invasion and migration of HCC stem cells, the CD133+ CD44 + HCC stem cells were sorted and treated with the mimic or inhibitor of miR-448, small interfering RNA (siRNA) against MAGEA6 or an AMPK activator AICAR. MAGEA6 silencing or miR-448 overexpression was demonstrated to inhibit the abilities of sphere formation, colony formation, cell migration, and invasion of HCC cells. Afterwards, a rescue experiment was conducted and revealed that MAGEA6 silencing reversed the effects of miR-448 inhibitor on stemness maintenance and self-renewal of HCC stem cells. Finally, after the in vivo experiment was carried out, miR-448 was observed to restrain the tumor formation and stemness in vivo. Altogether, miR-448 activates the AMPK signaling pathway by downregulating MAGEA6, thus inhibiting the stemness maintenance and self-renewal of HCC stem cells, which identifies miR-448 as a new therapeutic strategy for HCC.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Antigens, Neoplasm/metabolism , Carcinoma, Hepatocellular/enzymology , Cell Self Renewal , Liver Neoplasms/enzymology , MicroRNAs/metabolism , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/enzymology , Animals , Antigens, Neoplasm/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , Neoplasm Proteins/genetics , Neoplastic Stem Cells/pathology , Signal TransductionABSTRACT
OBJECTIVE: To investigate residents' psychological stress factors and research the correlation between post-traumatic stress disorder (PTSD) and platelet 5-HT concentrations so as to provide scientific bases for diagnosis and treatment of PTSD and psychological intervention for people in the disaster area. METHODS: A questionnaire survey of 5500 residents who have accepted psychological help was conducted by the emphatic investigation method. While high performance liquid chromatography was used to detect the platelet serotonin concentration of 100 PTSD patients and 100 healthy people. RESULTS: (1) Of the 5114 cases, 3167 (61.93%) showed positive results in screening for psychological stress symptoms, and 399 (7.8%) were tested having apparent PTSD symptoms. Male and female prevalence showed no significant difference (χ(2) = -0.380, P = 0.704). The differences of prevalence between different age groups were statistically significant (χ(2) = 381.89, P = 0.000). (2) The differences in the level of platelet 5-HT between PTSD patients and normal control group were statistically significant. CONCLUSIONS: The typhoon of Hainan Province caused relatively large psychological problems to the disaster victims. Compared with normal control group, the platelet 5-HT levels of PTSD patients in the disaster areas are lower. It may be related to incidents exposure levels, cultural background, religious ideas, social concerns and psychological rescue of the residents who live in the disaster areas of Hainan.
