Exosome-derived microRNA-29c Induces Apoptosis of BIU-87 Cells by Down Regulating BCL-2 and MCL-1

Background: Aberrant expression of the microRNA-29 family is associated with tumorigenesis and cancerprogression. As transport carriers, tumor-derived exosomes are released into the extracellular space and regulatemultiple functions of target cells. Thus, we assessed the possibility that exosomes could transport microRNA-29c as a carrier and correlations between microRNA-29c and apoptosis of bladder cancer cells. Materials and
Methods: A total of 28 cancer and adjacent tissues were examined by immunohistochemistry to detect BCL-2and MCL-1 expression. Disease was Ta-T1 in 12 patients, T2-T4 in 16, grade 1 in 8, 2 in 8 and 3 in 12. Theexpression of microRNA-29c in cancer tissues was detected by quantitative reverse transcriptase PCR (QRTPCR).An adenovirus containing microRNA-29c was used to infect the BIU-87 human bladder cancer cell line.MicroRNA-29c in exosomes was measured by QRT-PCR. After BIU-87 cells were induced by exosomes-derivedmicroRNA-29c, QRT-PCR was used to detect the level of microRNA-29c. Apoptosis was examined by flowcytometry and BCL-2 and MCL-1 mRNA expressions were assessed by reverse transcription-polymerase chainreaction. Western blotting was used to determine the protein expression of BCL-2 and MCL-1.
Results: Theexpressions of BCL-2 and MCL-1 protein were remarkably increased in bladder carcinoma (p<0.05), but wasfound mainly in the basal and suprabasal layers in adjacent tissues. The expression of microRNA-29c in cancertissues was negatively correlated with the BCL-2 and MCL-1. The expression level of microRNA-29c in exosomesand BIU-87 cells from the experiment group was higher than that in control groups (p<0.05). Exosome-derivedmicroRNA-29c induced apoptosis (p<0.01). Although only BCL-2 was reduced at the mRNA level, both BCL-2and MCL-1 were reduced at the protein level.
Conclusions: Human bladder cancer cells infected by microRNA-29c adenovirus can transport microRNA-29c via exosomes. Moreover, exosome-derived microRNA29c inducesapoptosis in bladder cancer cells by down-regulating BCL-2 and MCL-1.