MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein 
expression by cleaving or repressing the translation of target mRNAs. In mammal 
animals, their function mainly represses the target mRNAs transcripts via 
imperfectly complementary to the 3'UTR of target mRNAs. Several miRNAs have been 
recently reported to be involved in modulation of glioma development, especially 
some up-regulated miRNAs, such as microRNA-21 (miR-21), which has been found to 
function as an oncogene in cultured glioblastoma multiforme cells. Temozolomide 
(TMZ), an alkylating agent, is a promising chemotherapeutic agent for treating 
glioblastoma. However, resistance develops quickly and with high frequency. To 
explore the mechanism of resistance, we found that miR-21 could protect human 
glioblastoma U87MG cells from TMZ induced apoptosis. Our studies showed that TMZ 
markedly enhanced apoptosis in U87MG cells compared with untreated cells 
(P<0.05). However, over-express miR-21 in U87MG cells could significantly reduce 
TMZ-induced apoptosis (P<0.05). Pro-apoptotic Bax and anti-apoptotic Bcl-2 
proteins are known to regulate the apoptosis of glioma cells. Bcl-2, resistance 
to induction of apoptosis, constitutes one major obstacle to chemotherapy in 
many cancer cells. Bax is shown to correlate with an increased survival of 
glioblastoma multiforme patients. Further research demonstrated that the 
mechanism was associated with a shift in Bax/Bcl-2 ratio and change in caspase-3 
activity. Compared to control cells, cells treated with TMZ showed a significant 
increase in the Bax/Bcl-2 ratio and caspase-3 activity (P<0.01). However, such 
effect was partly prevented by treatment of cells with miR-21 overexpression 
before, which appeared to downregulate the Bax expression, upregulate the Bcl-2 
expression and decrease caspase-3 activity. Taken together, these results 
suggested that over-express miR-21 could inhibit TMZ-induced apoptosis in U87MG 
cells, at least in part, by decreasing Bax/Bcl-2 ratio and caspase-3 activity, 
which highlighted the possibility of miR-21 overexpression in the clinical 
resistance to chemotherapeutic therapy of TMZ.