Circular RNA Sirtuin1 represses pulmonary artery smooth muscle cell proliferation, migration and autophagy to ameliorate pulmonary hypertension via targeting microRNA-145-5p/protein kinase-B3 axis

Abstract

Recently, several studies have been clarified that circular RNA (circRNA) was a vital regulatory gene of pulmonary hypertension (PH). Nevertheless, the action of circRNA in PH was not yet explored. This study was to figure out the biological function and potential molecular mechanism of circSirtuin1 (SIRT1) in PH. Construction of the PH rat model and hypoxia pulmonary artery smooth muscle cells (PASMC) model was performed, and test of circSIRT1/microRNA (miR)-145-5p/protein kinase-B3 (Akt3) was conducted. The influence of the circSIRT1/miR-145-5p/Akt3 axis on the histopathology, hemodynamics with autophagy of the pulmonary artery in rats was examined. Additionally, the impact of circSIRT1/miR-145-5p/Akt3 on the proliferation, migration and apoptosis with autophagy of PASMC under hypoxic environment was also determined. The targeting of circSIRT1/miR-145-5p/Akt3 was testified. The results manifested that circSIRT1 and Akt3 were elevated in PH, while miR-145-5p was declined. Knockdown of circSIRT1 ameliorated rat PH, suppressed PASMC proliferation, migration with autophagy in hypoxic environment. CircSIRT1 competitively combined with miR-145-5p to mediate Akt3. To sum up, circSIRT1/miR-145-5p/Akt3 was supposed to perform as a prospective molecular target for the treatment of PH.

Ginsenoside Rg3 overcomes tamoxifen resistance through inhibiting glycolysis in breast cancer cells

“…Cell apoptosis quantitative measurements were carried out using annexin V to test the phosphatidylserine exposure of cell membranes (Jing et al, 2022). MCF‐7 and MCF‐7/TamR cells were starved in the absence of FBS for 6 h. The cells were washed three times with PBS and incubated with binding buffer containing annexin V and PI.…”

Insights into circular RNAs: Biogenesis, function and their regulatory roles in cardiovascular disease

“…For example, circRNA‐calmodulin 4 (circ‐calm4) circ‐calm4 and circRNA‐glutamate metabotropic receptor 1 (circ‐Grm1) promote PASMCs proliferation and migration by regulating the circ‐calm4/miR‐337‐3p/myosin 10 signalling pathway and the circ‐Grm1/Grm1/repressor/activator protein‐1 (RAP1) axis, respectively 143,144 . Additionally, a recent study showed that CircSIRT1 was elevated in a rat model of PAH, while injection of the sh‐circSIRT1 lentiviral vector ameliorated PAH in rats 145 . Mechanistically, the knockdown of CircSIRT1 inhibited proliferation, migration and autophagy in hypoxic PASMCs by regulating the miR‐145‐5p/Akt3 pathway.…”

“… 143 , 144 Additionally, a recent study showed that CircSIRT1 was elevated in a rat model of PAH, while injection of the sh‐circSIRT1 lentiviral vector ameliorated PAH in rats. 145 Mechanistically, the knockdown of CircSIRT1 inhibited proliferation, migration and autophagy in hypoxic PASMCs by regulating the miR‐145‐5p/Akt3 pathway. Overall, previous studies have confirmed that circRNAs play an important role in PAH (Table 4 ).…”

The Landscape of Noncoding RNA in Pulmonary Hypertension

“…CircRNA circSIRT1 expression was elevated in lung tissues in a PH rat model and PASMCs exposed to hypoxia. Silencing of circSIRT1 prevented the development of PH in vivo and suppressed PASMCs proliferation, migration and autophagy in the hypoxic condition in vitro via circSIRT1/miR-145-5p/Akt3 [ 143 ]. These above studies investigated the in vivo therapeutic effect of circRNAs and identified different molecular mechanisms and functional roles of circRNA acting as ceRNA.…”