ABSTRACT
MicroRNAs (miRNAs) play an important role in drug resistance and modulate the efficiency of chemotherapy. A recent study indicated that miR-340 functions as a tumor suppressor in various types of cancer. However, the role of miR-340 in chemotherapy has not been reported yet. In this study, we found that miR-340 enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and MDR1. We further explored the mechanism underlying the promoting effects of miR-340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in the 3′ untranslated region of lysophosphatidic acid acyltransferase (LPAATβ) using the online program Targetscan (http://www.microrna.org). Luciferase reporter assays showed that miR-340 binds to the 3′UTR of LPAATβ. Enforced expression of miR-340-5p decreased the accumulation of LPAATβ in both MG-63 and Saos-2 cells. Silencing LPAATβ decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression of LPAATβ compromised the effects of miR-340-5p on CDDP-induced cell death and accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p enhanced the sensitivity to CDDP by targeting LPAATβ.
Subject(s)
Humans , Acyltransferases/physiology , Antineoplastic Agents/pharmacology , Bone Neoplasms/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm/physiology , MicroRNAs/physiology , Osteosarcoma/drug therapy , Acyltransferases/analysis , Acyltransferases/drug effects , Apoptosis/drug effects , Blotting, Western , Bone Neoplasms/physiopathology , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation , Drug Resistance, Neoplasm/drug effects , Luciferases , MicroRNAs/analysis , MicroRNAs/drug effects , Osteosarcoma/physiopathology , Real-Time Polymerase Chain ReactionABSTRACT
In order to make urban-rural comparison of the prevalence of hepatitis B and C virus (HBV and HCV, respectively) infection in China, a twin survey was conducted in 1996 on two groups (50 subjects each) of 21-55 year-old, apparently healthy women for infection markers and serum enzyme levels; one group (the urban group) was in Jinan, the provincial capital of Shandong Province, and the other (the rural group) was in a farming village in Zhangqiu area some 30 km away from Jinan City. Comparison between the two groups showed that there was no significant (p > 0.10) difference in the prevalence of HBsAg+, anti-HBs+, anti-HBc+ and the cases positive to any of three HBV infection markers (i.e. HBV+). No age-dependent difference was detected within or between the groups. Thus the overall positivity rate was 8% for HBsAg+, 47% for anti-HBs+, 48% for anti-HBc+, and 64% for HBV+. No anti-HCV+ case was found either in the urban group or in the rural group. Liver function remained normal in all cases studied. The results together with perusal of published data suggest the urban-rural difference will not be remarkable, if present, in HBV and HCV infection in the regions studied, and possibly in China as a whole.