RETRACTED: ANXA3 Silencing Ameliorates Intracranial Aneurysm via Inhibition of the JNK Signaling Pathway

Abstract

Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), β-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs.

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data

“…It is notable that, on one hand, improved tumour‐cell survival and proliferation was shown to be mediated, in part, by ANXA3‐mediated caspase 3 (CASP3) suppression 45,50,51 . And in vascular smooth muscle cells a decrease in CASP3 levels was also shown to accompany inhibition of apoptosis and increased proliferation induced by ANXA3 52 . On the other hand, CASP3 is also well‐known to mediate neutrophil programmed cell death: indeed over 1000 records being returned by the PubMed query: neutrophil* AND (‘Caspase 3’ OR CASP3) 53–57 .…”

“…45,50,51 And in vascular smooth muscle cells a decrease in CASP3 levels was also shown to accompany inhibition of apoptosis and increased proliferation induced by ANXA3. 52 On the other hand, CASP3 is also well-known to mediate neutrophil programmed cell death: indeed over 1000 records being returned by the PubMed query: neutrophil* AND ('Caspase 3' OR CASP3). [53][54][55][56][57] Specifically, implications in the regulation of The predominance of a given colour in a diagram indicates a tendency of expression of the Annexin family member to be preferentially restricted to a given leucocyte population.…”

Identification of biomarkers in common chronic lung diseases by co-expression networks and drug-target interactions analysis

“…Additionally, ANXA3 is a part of the Annexin family and binds to the phospholipids in a Ca 2+dependent manner. It also plays a vital role as a mediator in cellular growth, signal transduction pathways, cancer proliferation, invasion, and migration (Wang et al 2019e). Therefore, LMO7, TSPAN13, LAMA3, and ANXA3 are suggested as the candidates in COPD-IPF.…”

Annexin A3 and cancer (Review)

“…Thus, ANXA3 expression promotes HCC and lung cancer via the JNK signalling pathway (74). Another study reported that ANXA3 silencing ameliorates the intracranial aneurysm by inhibiting the JNK signalling pathway (75). Thus, ANXA3 may exert its role in different types of cancer and diseases via the JNK signalling pathway.…”