Fig. 6: The resistance to hypoxia conferred by Neat1 knock down can be reversed by increasing the levels of mature miR-22. | Cell Death & Disease

Fig. 6: The resistance to hypoxia conferred by Neat1 knock down can be reversed by increasing the levels of mature miR-22.

From: Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing

Fig. 6

a Quantification of Caspase 3/7 activity in iPS-CM transfected with siScr or siNEAT1 and increasing doses of pre-miR-22 and grown in hypoxic conditions. *p < 0.05 comparing cells transfected with siScr and grown in normoxic and hypoxic conditions. #p < 0.05 comparing cells transfected with siScr and siNEAT1 in hypoxia. §§§p < 0.001 comparing cells transfected with siNEAT1 with and without 1, 10, or 40 nM pre-miR-22, respectively. Results are based on three separate experiments with 3–6 replicates in each group. The mean and standard deviation for each group is indicated. b Proposed mechanism by which Neat1 indirectly affects the sensitivity of cardiomyocytes to hypoxia. The two Neat1 isoforms (denoted Neat1_V1 and Neat1_V2) form the structural basis of paraspeckles together with NONO/SFPQ heterodimers. Neat1 recruits the Microprocessor complex (formed by DGCR8 and DROSHA) according to the model described by Jiang et al. and is required for efficient processing of pri-miR-22 in cardiomyocytes. Decreased Neat1 levels in response to hypoxia leads to disruption of paraspeckles and an accumulation of unprocessed pri-miR-22 in the nucleus. The subsequent decrease in biologically active miR-22 in the cytoplasm renders cardiomyocytes less sensitive to hypoxia, possibly through derepression of validated mRNA targets such as SIRT1 and HIF1A.

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