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bioRxiv · 10.1101/2024.01.25.577303

LncRNA-CIR6 Mediates Repair of Infarcted Hearts by Inducing MSCs Differentiation into Cardiogenic Cells through CDK1

Cui, X.·Dong, H.·Luo, S.·Zhuang, B.·Li, Y.·Zhong, C.·Ma, Y.·Cheng, X. W.·Hong, L.
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Abstract

PurposeThis study aims to investigate the induction effect of LncRNA-CIR6 on MSCs differentiation into Cardiogenic Cells in vitro and in vivo. MethodsIn addition to pretreatment with the Ro-3306 (CDK1 inhibitor), LncRNA-CIR6 was transfected into BMSCs and hUCMSCs using jetPRIME. LncRNA-CIR6 was transfected into C57BL/6 mice heart by 100 L of AAV9-cTnT-LncRNA-CIR6-ZsGreen i.v. After 3 weeks of transfection followed by AMI surgery, hUCMSCs (5x105/100 L) were injected by i.v 1 week later. Cardiac function was evaluated using VEVO 2100 and electric mapping 9 days after cell injection. IF, Evans blue-TTC, Masson staining, FACS, and WB were used to determine relevant indicators. ResultsLncRNA-CIR6 induced a significant percentage of differentiation in BMSCs (83.00{+/-}0.58)% and hUCMSCs (95.43{+/-}2.13)% into cardiogenic cells, as determined by the expression of cTnT. Compared with MI group, cardiac contraction and conduction function in MI heart treated by LncRNA-CIR6 or combined with MSCs injection groups were significantly increased as well as the area of MI and fibrosis were significantly lower. The transcriptional expression region of LncRNA-CIR6 was in Chr17 from 80209290 to 80209536. The functional region of LncRNA-CIR6 was located at nucleotides 0-50/190-255 in the sequence. CDK1 is a protein found to be related to the proliferation and differentiation of cardiomyocytes is which located in the functional region of LncRNA-CIR6 secondary structure (from 0 to 17). Ro-3306 impeded the differentiation of MSCs into cardiogenic cells, while MSCs transfected with LncRNA-CIR6 showed high expression of CDK1. LncRNA-CIR6 mediates repair of infarcted hearts by inducing MSCs differentiation into cardiogenic cells through CDK1. ConclusionsLncRNA-CIR6 mediates repair of infarcted hearts by inducing MSCs differentiation into cardiogenic cells through CDK1.

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Cui, X., Dong, H., Luo, S., Zhuang, B., Li, Y., Zhong, C., Ma, Y., Cheng, X. W., Hong, L.. 2024-01-28. LncRNA-CIR6 Mediates Repair of Infarcted Hearts by Inducing MSCs Differentiation into Cardiogenic Cells through CDK1. https://doi.org/10.1101/2024.01.25.577303

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