Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis

He, Xiang; Wang, Shifei; Li, Mengsha; Zhong, Lintao; Zheng, Hao; Sun, Yili; Lai, Yanxian; Chen, Xiaoqiang; Wei, Guoquan; Si, Xiaoyan; Han, Yanming; Huang, Suming; Li, Xinzhong; Liao, Wangjun; Liao, Yulin; Bin, Jianping

doi:10.7150/thno.34463

Cited by 68 publications

(48 citation statements)

References 41 publications

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“…Apoptosis induced by GAS5 was certified by several tumor researches (Liu et al, 2018;Gao et al, 2019;He et al, 2019;Zhou et al, 2019), but in this study, we didn't detect apoptosis inducing effect of GAS5 after transfection. The cell line specificity might be the reason of this discrepancy.…”

Section: Discussionmentioning

confidence: 77%

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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Preeclampsia is a lethal pregnancy specific hypertensive disorder involving multisystem. Despite extensive studies to investigate the causes of preeclampsia, the pathogenesis still remains largely unknown. Long non-coding RNAs (lncRNAs) are a diverse class of non-translated RNAs which play a crucial part in various biological phenomena. Although lncRNA Growth Arrest-Specific 5 (GAS5) aberrantly expressed in multiple cancer tissues and is implicated in multiple biological processes of tumor cells, little is known about its role in preeclampsia. In this study, 40 patients with preeclampsia and 32 gestational age matched normotension pregnant women were recruited. Using quantitative real-time polymerase chain reaction (qRT-PCR), we found higher expression of GAS5 in placenta of preclamsia affected women. The level of GAS5 existed strongly in correlation with Thrombin Time indicating coagulation function and other clinical parameters by Pearson correlation analysis. Then we constructed the GAS5 lentivirus expression vectors and transfected into human trophoblast cell lines HTR-8/SVneo and JEG-3. Using in vitro cell culture studies, we found an inhibited effect of GAS5 on proliferative ability, migratory ability and invasive ability however; no effect on apoptosis was detected. Further mechanistic analysis found that GAS5 modulated microRNA-21 (miR-21) in an opposite variation tendency by qRT-PCR and rescue experiment. In addition, inhibition of GAS5 promoted the activation of PI3K/AKT signaling pathway and its downstream proteins covering MMP-9 and TP53 as evident from our qRT-PCR and western blot analyses. Thus, we suggested that GAS5 might involve in pregnancy with preeclampsia by influencing the biological functions of trophoblast cells through the regulation of miR-21 and activation of PI3K/AKT signaling pathway and its downstream targets, which may contribute to reveal the nature of preeclampsia.

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Section: Discussionmentioning

confidence: 77%

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Zheng

Hou

et al. 2020

Front. Genet.

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“…In addition to its roles as an RNA binding protein, YBX1 also functions as a transcription factor 58 . Previous studies showed lncRNA can bind to YBX1 and influence the transcriptional activities of YBX1 59 .…”

Section: Resultsmentioning

confidence: 99%

LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network

et al. 2020

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Rationale: The forkhead box A1 (FOXA1) is a crucial transcription factor in initiation and development of breast, lung and prostate cancer. Previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes. Its regulatory network of long non-coding RNAs (lncRNAs) and their role in FOXA1 oncogenic activity remains unknown. Methods: The Cancer Genome Atlas (TCGA) data, RNA-seq and ChIP-seq data were used to analyze FOXA1 regulated lncRNAs. RT-qPCR was used to detect the expression of DSCAM-AS1, RT-qPCR and Western blotting were used to determine the expression of FOXA1, estrogen receptor α (ERα) and Y box binding protein 1 (YBX1). RNA pull-down and RIP-qPCR were employed to investigate the interaction between DSCAM-AS1 and YBX1. The effect of DSCAM-AS1 on malignant phenotypes was examined through in vitro and in vivo assays. Results: In this study, we conducted a global analysis of FOXA1 regulated lncRNAs. For detailed analysis, we chose lncRNA DSCAM-AS1, which is specifically expressed in lung adenocarcinoma, breast and prostate cancer. The expression level of DSCAM-AS1 is regulated by two super-enhancers (SEs) driven by FOXA1. High expression levels of DSCAM-AS1 was associated with poor prognosis. Knockout experiments showed DSCAM-AS1 was essential for the growth of xenograft tumors. Moreover, we demonstrated DSCAM-AS1 can regulate the expression of the master transcriptional factor FOXA1. In breast cancer, DSCAM-AS1 was also found to regulate ERα. Mechanistically, DSCAM-AS1 interacts with YBX1 and influences the recruitment of YBX1 in the promoter regions of FOXA1 and ERα. Conclusion: Our study demonstrated that lncRNA DSCAM-AS1 was transcriptionally activated by super-enhancers driven by FOXA1 and exhibited lineage-specific expression pattern. DSCAM-AS1 can promote cancer progression by interacting with YBX1 and regulating expression of FOXA1 and ERα.

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“…An increasing number of studies have demonstrated the direct role of lncRNAs in the pathogenesis of various human diseases including tumors, inflammatory, cardiovascular, and immunological diseases [ 3 , 5 ]. In many studies, the regulatory mechanism of lncRNAs in aortic aneurysms was also shown, which was directly associated with the formation, growth and dissection of the aorta ( Table 1 ) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In recent years, increasing studies have focused on role lncRNAs in the pathogenesis of IAs.…”

Section: Lncrnas and Iasmentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Intracranial Aneurysms and Subarachnoid Hemorrhage

Gareev

Beylerli

Aliev

et al. 2020

Life

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Intracranial aneurysms (IAs) represent the most complex and relevant problem of modern neurology and neurosurgery. They serve as one of the main causes of non-traumatic subarachnoid hemorrhage (SAH), causing up to 85% of all cases of intracranial hemorrhage, which is associated with frequent disability and high mortality among patients. Unfortunately, the molecular mechanisms of the development and rupture of IAs are still under study. Long non-coding RNAs (lncRNAs) are non-coding RNAs that typically have a length of more than 200 nucleotides. It is known that lncRNAs regulate many processes, such as transcription, translation, cell differentiation, regulation of gene expression, and regulation of the cell cycle. In recent years, a lot of evidence has established their role in human diseases from oncology to cardiovascular disease. Recent studies have shown that lncRNAs may be involved in the pathogenesis of IAs. The study of lncRNAs and its targets in various pathological conditions of a person is a rapidly developing field, and it is likely that the knowledge obtained from these studies regarding the pathogenesis of intracranial aneurysms will have the potential to use lncRNAs in therapy, as well as in the diagnosis and prediction of high aneurysms risk of rupture.

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Long noncoding RNA GAS5 induces abdominal aortic aneurysm formation by promoting smooth muscle apoptosis

Cited by 68 publications

References 41 publications

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21

LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network

The Role of Long Non-Coding RNAs in Intracranial Aneurysms and Subarachnoid Hemorrhage

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