High-throughput sequencing analysis of lncRNAs in hippocampus tissues with hypoxic-ischemic brain damage.

Int J Clin Exp Pathol 2018 1;11(11):5265-5277. Epub 2018 Nov 1.

Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine Nanjing, China.

LncRNAs abundantly expressed in the brain have vital and wide-ranging functions in different biological processes. However, little is currently known regarding the influence of lncRNAs in developing brains after hypoxic-ischemic brain damage (HIBD). In this study, to investigate the lncRNAs expression signatures and the co-expression network of lncRNAs and mRNAs in the brain after HIBD, we established a and detected the expression profiles of lncRNAs in the HIBD brain and a sham control using high-throughput sequencing. Further, highly differentially expressed lncRNAs were selected and validated by qRT-PCR. Finally, the biological functions of the selected lncRNAs were investigated by over-expressing or silencing the target genes through lentivirus transfection in hippocampal neuron cells. Our results revealed that the expression profile of lncRNAs was dramatically different between the HIBD brains and the sham control, showing as the aberrant expression of 617 lncRNA transcripts and 441 mRNA transcripts at 24 hours after HIBD. GO and KEGG analyses indicated that the differentially expressed mRNAs were mostly involved in the apoptosis signaling pathway. After validating the expression of 8 randomly selected lncRNA transcripts by qRT-PCR, we found that the gene (ID: ENSRNOG00000021987) was down-regulated in HI brains. After stable over-expression and silencing of , the apoptosis rate of hippocampal neuron cells exhibited obvious changes under hypoxia or normaxia. The over-expression of could significantly up-regulate Bcl-2 but down-regulate Bax, caspase-3, and caspase-9 at the mRNA and protein levels, while the silencing of led to just the opposite phenomenon. Notably, the regulation effects of on apoptotic related genes and proteins under hypoxia were more obvious than those under normaxia. Moreover, the over-expression of reduced the apoptotic rate, but the loss of led to a high rate of apoptosis under hypoxia. Taken together, the silencing of exacerbated, while over-expression attenuated, neuron apoptosis induced by HI injury, suggesting that may be a target for the prognosis, diagnosis, and treatment of HIBD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963025PMC
November 2018

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