&lt;p&gt;Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer&lt;/p&gt;

Yu, Yaya; Hann, Swei Sunny

doi:10.2147/ott.s221305

Cited by 42 publications

(28 citation statements)

References 143 publications

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“…The invasion of trophoblasts and the invasion of tumor cells share similar biological behaviors (West et al, 2018). GAS5 expression which is found to be decreased in tumor tissues (Yu and Hann, 2019) has been proved to increase in preeclampsia placenta in our work firstly, especially with the highest level in early-onset, which is consistent with the pathological feature of insufficient trophoblast invasion. However, placenta development is a sequential process, samples are only available at the end of pregnancy.…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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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“…The present study is the first to demonstrate the positive correlation between GAS5 and ULK1/2 levels in BC pathogenesis, to the best of the authors' knowledge. GAS5 is not only expressed in multiple cancers including breast cancer, but also widely expressed in a variety of normal tissues, such as lung, esophagus, colon, ovary and kidney (26). GAS5 is involved in the regulation of physiological processes; for example, GAS5 transcriptionally regulates mTOR and thus activates downstream signaling, which promotes cell proliferation by promoting entry into the G 2 /M phase of the cell cycle (27).…”

Section: Discussionmentioning

confidence: 99%

“…In these cancer types, GAS5 was revealed to be transcriptionally downregulated, and GAS5 upregulation inhibited malignant behaviors, including proliferation, migration, invasion and tumor formation. Given these reports, several studies investigating GAS5 have aimed to increase cellular GAS5 levels via specific methods to control the proliferation of cancer cells ( 26 , 7 , 14 ). In the present study, it was reported that the expression levels of GAS5 were significantly downregulated in BC clinical samples compared to those in adjacent normal samples, and the expression of GAS5 was positively correlated with the expression levels of ULK1 and ULK2, which are key initiators of autophagy ( 20 – 22 ).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA growth arrest‑specific 5 (GAS5) acts as a tumor suppressor by promoting autophagy in breast cancer

Li¹,

Lin

Tang

et al. 2020

Mol Med Rep

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Growth arrest-specific 5 (GAS5) is a known tumor suppressor which negatively regulates cell survival and malignancy in several cancer cell types. The present study aimed to establish the correlation between GAS5 and unc-51 like autophagy activating kinase (ULK)1/2, two key regulators of autophagy initiation in breast cancer (BC). To address this, expression levels of these genes were quantitively analyzed in BC clinical samples by performing reverse transcription-quantitative PCR. GAS5 was downregulated in BC clinical samples compared with adjacent samples and was positively correlated with ULK1/2. Detection methods including cell cycle analysis, annexin V-FITC/PI double staining and flow cytometry analysis, Transwell cell invasion assay, transfection and western blotting were used for BC cells. In MCF-7 cells, it was also observed that overexpression of GAS5 upregulated ULK1/2 protein levels without disturbing other autophagy initiation-associated proteins and inhibited cell proliferation, invasion and tumor formation. These effects were reversed by blocking autophagy with 3-methyladenine (3-MA). These results demonstrated that the suppressive effects of overexpressed GAS5 were mediated via autophagy induction, at least in part. Overexpression of GAS5 induced chemoresistance to cisplatin, which was not reversed by 3-MA-mediated inhibition of autophagy, indicating that GAS5 promotes chemosensitivity in an autophagy-independent manner. Collectively, these results indicated that GAS5 contributes to the pathogenesis of BC potentially by promoting autophagy. However, the mechanism by which GAS5 functions as a tumor suppressor in an autophagy-independent manner remains unknown.

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“…It was therefore indicated that lncRNA GAS5 may be a suppressor for AS. In addition, studies have found that the expression of lncRNA GAS5 is reduced in most tumour types ( 36 ), including prostate cancer, renal cell carcinoma, ovarian cancer, cervical cancer and osteosarcoma. Of note, the occurrence of tumours is associated with the immune inflammatory microenvironment, mainly manifested as chronic inflammation ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis

et al. 2020

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The present study aimed to investigate the expression and significance of the mRNA of genes associated with autophagy and long non-coding RNA (lncRNA) GAS5 in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS). The mRNA levels of microtubule-associated protein light chain 3 (LC3), Beclin1, autophagy-related gene (ATG)3, ATG5, ATG12, ATG 16 ligand 1 (ATG16L1) and lncRNA growth arrest-specific 5 (GAS5) in PBMCs from 60 patients with AS and 30 healthy controls (HC) were examined by reverse transcription-quantitative PCR. The correlations between the levels of LC3, Beclin1, ATG3, ATG5, ATG12 and ATG16L1 mRNA as well as lncRNA GAS5 levels with disease activity and laboratory parameters in patients with AS were determined by Spearman correlation analysis. In addition, the diagnostic value of lncRNA GAS5 for AS was explored through establishing a receiver operating characteristic (ROC) curve. The results indicated that, compared to the HCs, patients with AS had lower expression levels of LC3, ATG5, ATG12, ATG16L1 and lncRNA GAS5 in their PBMCs. Compared with those in patients with inactive AS, the levels of ATG5 and ATG12 were lower than those in patients with active AS. Of note, ATG5 and ATG12 mRNA levels were negatively correlated with disease activity indexes. lncRNA GAS5 was positively correlated with the expression of Beclin1, ATG3, ATG5, ATG12 and ATG16L1. The area under the ROC curve for the use of lncRNA GAS5 expression to diagnose AS was 0.808 with a 95% CI of 0.714-0.902. In conclusion, patients with AS had decreased expression of genes associated with autophagy and lncRNA GAS5. The extent of the reduction in ATG5 and ATG12 expression levels in patients with AS was correlated with the disease severity and activity. Furthermore, lncRNA GAS5 was a diagnostic indicator of AS.

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<p>Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer</p>

Cited by 42 publications

References 143 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

Long non‑coding RNA growth arrest‑specific 5 (GAS5) acts as a tumor suppressor by promoting autophagy in breast cancer

Autophagy dysfunction may be involved in the pathogenesis of ankylosing spondylitis

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