Rian/miR-210-3p/Nfkb1 Feedback Loop Promotes Hypoxia-Induced Cell Apoptosis in Myocardial Infarction Through Deactivating the PI3K/Akt Signaling Pathway

Abstract

Myocardial infarction (MI) is a severe disease that could lead to reversible or irreversible ischemic heart damage. A previous study has revealed that microRNA mmu-miR-210-3p expression is downregulated in fat-1 transgenic mice post-MI. Nevertheless, the specific mechanism of miR-210-3p in MI remains obscure. In this study, we observed that miR-210-3p expression was downregulated in the mice's left ventricle post-MI, and miR-210-3p expression was suppressed while cell apoptosis was promoted in H9c2 cells under hypoxia condition. Besides, miR-210-3p overexpression could enhance cell proliferation and inhibit cell apoptosis in hypoxia-treated H9c2 cells. Then, molecular mechanism assays revealed that miR-210-3p overexpression could activate the PI3K/Akt pathway, and nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1) was the target of miR-210-3p. In addition, RNA imprinted and accumulated in nucleus (Rian), a long noncoding RNA, could sponge miR-210-3p to upregulate Nfkb1 expression. Besides, Nfkb1 was verified to facilitate the transcription of Rian by binding with a Rian promoter. Furthermore, rescue assays revealed that both Nfkb1 and PI3K/Akt pathway are engaged in the Rian-mediated cell proliferation and apoptosis in hypoxia-treated H9c2 cells. In conclusion, a Rian/miR-210-3p/Nfkb1 feedback loop enhances hypoxia-induced cell apoptosis in MI through deactivating the PI3K/Akt pathway.

Long non‑coding RNA Rian protects against experimental bronchopulmonary dysplasia by sponging miR‑421

“…A study by Cai et al (38) demonstrated that lncRNA gallbladder cancer drug resistance-associated lncRNA1 (GBCDRlnc1) induces chemoresistance of gallbladder carcinoma cells by activating autophagy. Several studies have demonstrated that Rian is an important regulator of biological processes (15,(17)(18)(19). However, the role of lncRNA Rian in BPD has remained to be fully explored.…”

“…RNA imprinted and accumulated in nucleus (Rian) is an lncRNA with a parent-specific expression, which is located on mouse chromosome 12 and includes three long transcripts: Irm, Meg8 and AB063319 (15,16). A large number of studies have revealed that Rian is a vital regulator of multiple biological processes (15,17,18). For instance, Yao et al (17) indicated that the upregulation of lncRNA Rian suppressed cell apoptosis from cerebral ischemia-reperfusion injury through Rian/miR-144-3p/GATA binding protein 3 signaling.…”

Regulatory Networks, Management Approaches, and Emerging Treatments of Nonalcoholic Fatty Liver Disease

“…Rian, a small RNA, could regulate numerous target genes, and the human homologs of some of these microRNAs have been proposed to both stimulate and inhibit tumorigenesis in other types of malignancies. Rian/miR-210-3p/NF- κ B1 (the target of miR-210-3p) feedback loop inactivates the PI3K/Akt pathway [ 125 ], suggesting a direct link between NF- κ B1 and PIK3/Akt pathway. In general, the role of LEP and NF- κ B is reciprocal; LEP can directly activate NF- κ B signaling, while NF- κ B can indirectly regulate LEP through JAK-STAT, PI3K/AKT, and ERK signaling pathways.…”