STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

Abstract

Long noncoding RNAs (lncRNAs) were viewed as crucial participants in the pathogenesis of abdominal aortic aneurysm (AAA). LncRNA NEAT1 was recognized as an oncogenic gene in various diseases. However, its function and mechanism in AAA were not precisely documented. Here, we explored the functional role and molecular mechanism of NEAT1 in AAA. Functionally, the effect of NEAT1 on the proliferation was assessed by CCK-8 and EdU assay, while its impact on the apoptosis was evaluated through caspase-3/9 activity and TUNEL assays. As a result, we found that NEAT1 knockdown enhanced the proliferation and impaired the apoptosis of vascular smooth muscle cells (VSMCs). Reversely, overexpressed NEAT1 exerted anti-proliferation and pro-apoptosis effects in VSMCs. Mechanically, we found that STAT3 acted as a transcription factor and contributed to NEAT1 transcription by ChIP and luciferase reporter assays. In addition, NEAT1 was confirmed as a sponge of miR-4688 and thereby increase the expression of TULP3 in VSMCs via RIP assay and RNA pull-down assay. Rescue experiments indicted that TULP3 overexpressing countervailed the impact of NEAT1 depletion on AAA biological processes. Conclusively, lncRNA NEAT1 induced by STAT3 was identified as a ceRNA and facilitated AAA formation by targeting miR-4688/TULP3 axis.

Pathogenetic profiling of COVID-19 and SARS-like viruses

“…For instance, upregulation of MALAT1 ceases miR-155 expression which promotes GATA3 and Th2 cytokine production leading to severe asthma and loss of lung function [ 90 ]. On the other hand, LINC00265 inhibits let-7a activity using ceRNA mechanism, which results in the upregulation of IL6 [ 143 ]. All these eventually lead to the deterioration of lung tissues and successful viral replication [ 144 ].…”

The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression

“…In the study by Shuai Wang, the NEAT1 paraspeckle promoted the progression of human hepatocellular carcinoma by increasing IL-6/STAT3 signalling [ 53 ]. Moreover, STAT3 may function as one positive feedback regulator that induces the upregulation of NEAT1 as a competing endogenous RNAs (ceRNA) that then facilitates abdominal aortic aneurysm formation by targeting the miR-4688/TULP3 axis [ 20 ]. The forward signalling cascades and reverse feedback loop between NEAT1 and STAT3 have been verified in different tumours, and some tissue-specific or universal miRNAs will fill in the gap and form one tissue/tumour-specific NEAT1/miRNA/STAT3 axis for the indicated tumour.…”

“…For example, Arrighetti et al found that miR-483 overexpression in ovarian cancer interferes with the proliferation of these tumour cells by targeting PRKCA (encoding PKC-α) and subsequently protects them from platinum-induced DNA damage [ 19 ]. According to Che et al, miR-483 promotes proliferation, migration, and invasion and induces chemoresistance in Wilms tumour cells [ 20 ]. However, in some tumour types, such as glioma, osteosarcoma, breast cancer and angiosarcoma, miR-483 is downregulated, indicating that it also functioned as a tumour suppressor [ 21 – 23 ].…”

Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa

“…Jaspar prediction software was employed to further identify STAT binding motifs on the NEAT1 promoter region, with a minimum relative profile score threshold of 80% [ 51 ]. Among the potential binding motifs of STAT3 on the NEAT1 promoter, there was the one previously reported by Cai et al [ 52 ] that served as a basis to design DNA retardation assay probes ( Figure S2 ).…”