The increased proliferation and migration of airway smooth muscle cells (ASMCs) are critical processes in the formation of airway remodeling in asthma. Long non-coding RNAs (lncRNAs) have emerged as key mediators of diverse physiological and pathological processes, and are involved in the pathogenesis of various diseases, including asthma. LncRNA Malat1 has been widely reported to regulate the proliferation and migration of multiple cell types and be involved in the pathogenesis of various human diseases. However, it remains unknown whether Malat1 regulates ASMC proliferation and migration. Here, we explored the function of Malat1 in ASMC proliferation and migration in vitro stimulated by platelet-derived growth factor BB (PDGF-BB), and the underlying molecular mechanism involved. The results showed that Malat1 was significantly upregulated in ASMCs treated with PDGF-BB, and knockdown of Malat1 effectively inhibited ASMC proliferation and migration induced by PDGF-BB. Our data also showed that miR-150 was a target of Malat1 in ASMCs, and inhibited PDGF-BB-induced ASMC proliferation and migration, whereas the inhibition effect was effectively reversed by Malat1 overexpression. Additionally, translation initiation factor 4E (eIF4E), an important regulator of Akt signaling, was identified to be a target of miR-150, and both eIF4E knockdown and Akt inhibitor GSK690693 inhibited PDGF-BB-induced ASMC proliferation and migration. Collectively, these data indicate that Malat1, as a competing endogenous RNA (ceRNA) for miR-150, derepresses eIF4E expression and activates Akt signaling, thereby being involved in PDGF-BB-induced ASMC proliferation and migration. These findings suggest that Malat1 knockdown may present a new target to limit airway remodeling in asthma.
Mutations in ATP6 gene are frequent causes of mitochondrial encephalomyopathies. ATP6 gene encodes one subunit of complexⅤ. The present study described a missense mutation in ATP6 gene in a 8‐year‐old Chinese boy with mitochondrial encephalomyopathy. We identified one missense mutation in ATP6 gene (m.8914C>T) by mitochondrial DNA sequencing. This mutation altered the amino acid proline in serine, and alterative protein is predicted to be harmful. The mutation load in blood sample of patient is 59.49%. Activity of all mitochondrial complexes in blood are normal, however, the total function of mitochondrial oxidative phosphorylation were declined (including pathwayⅠ, pathwayⅡ and pathwayⅣ). The missense mutation (m.8914C>T) in ATP6 gene could result in abnormal function of complexV and is related with mitochondrial encephalomyopathy.
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