Combinatorial effects of miR-20a and miR-29b on neuronal apoptosis induced by spinal cord injury

• Published in: International journal of clinical and experimental pathology Vol. 8; no. 4; pp. 3811 - 3818
• Main Authors: Liu, Xue-Jun, Zheng, Xue-Ping, Zhang, Rui, Guo, Yun-Liang, Wang, Jian-Hong
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2015
• Subjects: Animals; Apoptosis - genetics; Cell Line, Tumor; Cell Survival; Down-Regulation; Female; Humans; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Myeloid Cell Leukemia Sequence 1 Protein - metabolism; Neurons - metabolism; Neurons - pathology; Original; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - pathology; Up-Regulation; spinal cord injury; Neuronal apoptosis; myeloid cell leukemia sequence-1; MicroRNAs
• ISSN: 1936-2625

Neuronal apoptosis is one of the prominent features involved in spinal cord injury (SCI). MicroRNAs (miRNAs) are small non-coding RNAs that functions in a variety of cellular processes including apoptosis. MiRNAs have been implicated as effectors of SCI. However, role of miRNAs in SCI-associated neuronal apoptosis remains to be investigated. A number of bioinformatics approaches have suggested Mcl-1 and BH3-only family genes as potential downstream targets regulated by miR-20a and miR-29b, respectively. To determine whether miR-20a and miR-29b play a role in neuronal apoptosis of SCI by regulating those genes, we transfected Neuro-2A neuroblastoma cells with mimic and inhibitor for the two miRNAs. The miR-20a mimic decreased Mcl-1 expression and the miR-29b mimic reduced the expression of Bad, Bim, Noxa and Puma. The repressor role of miR-20a and miR-29b is confirmed by the transfection of Neuro-2A cells with their inhibitor. Moreover, miR-20a mimic or miR-29b inhibitor attenuated Neuro-2A cell viability and co-transfection of both further diminished the viability of these cells. The in vitro effects of miR-20a and miR-29b on neuronal apoptosis were corroborated by the in vivo studies. Injection of miR-20a mimic or miR-29b inhibitor into the lesion of the injured spinal cord rescued the neuronal death and co-injection of both completely abolished SCI-induced apoptosis. In conclusion, altered expression of miR-20a and miR-29b may cooperatively contribute to the neuronal cell death of SCI through down-regulating anti-apoptotic myeloid cell leukemia sequence-1 (Mcl-1) and up-regulating pro-apoptotic BH3-only proteins.