MicroRNAs (
miRNAs) have been found to be involved in
cancer initiation, progression and
metastasis and, as such, have been suggested as tools for
cancer detection and
therapy. In this work, a large-scale screening of the complete
miRNA mimics library demonstrated that hsa-miR-15a-3p had a pro-apoptotic role in the following human
cancer cells: HeLa, AsPc-1, MDA-MB-231, KB3, ME180, HCT-116 and A549. MiR-15a-3p is a novel member of the pro-apoptotic
miRNA cluster, miR-15a/16, which was found to activate
Caspase-3/7 and to cause viability loss in B/CMBA.Ov cells during preliminary screening. Subsequent microarrays and bioinformatics analyses identified the following four anti-apoptotic genes: bcl2l1, naip5, fgfr2 and mybl2 as possible targets for the mmu-miR-15a-3p in B/CMBA.Ov cells. Follow-up studies confirmed the pro-apoptotic role of hsa-miR-15a-3p in human cells by its ability to activate
Caspase-3/7, to reduce cell viability and to inhibit the expression of bcl2l1 (bcl-xL) in HeLa and AsPc-1 cells. MiR-15-3p was also found to reduce viability in HEK293, MDA-MB-231, KB3, ME180, HCT-116 and A549 cell lines and, therefore, may be considered for apoptosis modulating
therapies in
cancers associated with high Bcl-xL expression (cervical, pancreatic, breast, lung and
colorectal carcinomas). The capability of hsa-miR-15a-3p to induce apoptosis in these
carcinomas may be dependent on the levels of Bcl-xL expression. The use of endogenous inhibitors of bcl-xL and other anti-apoptotic genes such as hsa-miR-15a-3p may provide improved options for apoptosis-modulating
therapies in
cancer treatment compared with the use of artificial
antisense oligonucleotides.