Down-regulation expression of TGFB2-AS1 inhibits the proliferation, migration, invasion and induces apoptosis in HepG2 cells

Liu, Wenrong; Huai, Rui-Ping; Yin, Zhang; Rao, Shuquan; Xiong, Lili; Ding, Ruofan; Mao, Canquan; Zhao, Wenqing; Hao, Tong; Huang, Qingqing; Guo, Zhiyun

doi:10.1007/s13258-019-00826-6

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Recent studies found the role of long non-coding RNA in doxorubicin-induced cardiomyopathy, lncRNA NONMMUT015745 inhibits doxorubicin-mediated cardiomyocytes apoptosis by regulating the Rab2A-p53 axis [27], METTL14 silencing suppresses the ferroptosis of cardiomyocyte in doxorubicin-induced mice[28].TGFB2-AS1 has been reported in breast cancer, glioma, lung adenocarcinoma, gastric cancer, and other tumor diseases, and more importantly, the limited molecular biological role of TGFB2-AS1 in some diseases has been illustrated [29]. Studies have shown that mutations in the TGFBR1 and TGFB2-AS1 genes were associated with myopia in preschoolers, mediated by the TGF-β signaling pathway [30]; loss of TGFB2-AS1 signi cantly promoted Apoptosis of HepG2 liver cancer cells and inhibited migration and invasion [31], and TGFB2-AS1 interacted with the Core subunit of SWI/SNF complex, SMARCA4 to inhibit the expression of target genes TGFB2 and SOX2, ultimately inhibiting the breast Cancer progression [32]. Evolutionary conservation is widely used as an indicator of the functional signi cance of newly discovered lncRNAs and the evolutionary conservation of lncRNAs is multidimensional including Sequence, structure, function, and syntenic expression, and different from the conserved analysis of coding gene proteins [33].…”

Section: Discussionmentioning

confidence: 99%

TGFB2-AS1 binding to MED1 promotes doxorubicin-induced cardiomyocyte apoptosis via BMP7 pathway

Gao,

Lan,

Peng

et al. 2024

Preprint

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Doxorubicin-induced cardiotoxicity (DIC) is similar to dilated cardiomyopathy (DCM) in morphological and functional defects, eventually progressing to heart failure. Recently, intensive investigation showed that specific expression profiles of lncRNA have been closely related to cardiovascular disease, but many gaps remain, including the emerging roles of lncRNA in DIC. We identified TGFB2-AS1 as a highly conserved regulator of DCM by reanalyzing publicly available RNA sequencing datasets from GEO and producing conservation scores of lncRNAs using PHAST software. TGFB2-AS1 expression is dramatically increased in murine and cell models, and TGFB2-AS1 has a pro-apoptotic effect in vitro. Moreover, TGFB2-AS1 mediated apoptosis via the BMP7 pathway by activating the Smad1/5/9 phosphorylation to upregulate the target gene expression Id2. Recombinant human bone morphogenetic protein (rhBMP-7) aggravates doxorubicin-induced cardiomyocyte apoptosis, and knockdown of BMP7 significantly reverses the pro-apoptotic effect of TGFB2-AS1 overexpression in vitro. Mechanistically, we found that TGFB2-AS1 combines with transcriptional co-activator MED1, promoting H3K27 acetylation modification level in the promoter of the BMP7 gene and then facilitating BMP7 transcription. Collectively, this study illuminates that TGFB2-AS1 is an evolutionarily conserved long noncoding RNA with a previously unappreciated role in promoting the apoptotic phenotype of DIC and sheds light on the more effective clinical application of doxorubicin.

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Section: Discussionmentioning

confidence: 99%

TGFB2-AS1 binding to MED1 promotes doxorubicin-induced cardiomyocyte apoptosis via BMP7 pathway

Gao,

Lan,

Peng

et al. 2024

Preprint

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“…MAPT-AS1 is at the anti-sense strand of the MAPT promoter region to regulate MAPT, and the overexpression of MAPT-AS1 was verified to predict better BC patient survival ( 46 ). TGFB2-AS1 is associated with tumorigenesis, and promotes migration and invasion of HepG2 cells ( 47 ), but inhibits migration and invasion of lung adenocarcinoma cells ( 48 ). Regrettably, the biological functions and prognostic presentation of TGFB2-AS1 in BC are still unclear.…”

Section: Discussionmentioning

confidence: 99%

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Tan

Zhou

et al. 2022

Front. Immunol.

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Aberrant glycosylation, a post-translational modification of proteins, is regarded to engage in tumorigenesis and malignant progression of breast cancer (BC). The altered expression of glycosyltransferases causes abnormal glycan biosynthesis changes, which can serve as diagnostic hallmarks in BC. This study attempts to establish a predictive signature based on glycosyltransferase-related lncRNAs (GT-lncRNAs) in BC prognosis and response to immune checkpoint inhibitors (ICIs) treatment. We firstly screened out characterized glycosyltransferase-related genes (GTGs) through NMF and WGCNA analysis and identified GT-lncRNAs through coexpression analysis. By using the coefficients of 8 GT-lncRNAs, a risk score was calculated and its median value divided BC patients into high-and low-risk groups. The analyses unraveled that patients in the high-risk group had shorter survival and the risk score was an independent predictor of BC prognosis. Besides, the predictive efficacy of our risk score was higher than other published models. Moreover, ESTIMATE analysis, immunophenoscore (IPS), and SubMAP analysis showed that the risk score could stratify patients with distinct immune infiltration, and patients in the high-risk group might benefit more from ICIs treatment. Finally, the vitro assay showed that MIR4435-2HG might promote the proliferation and migration of BC cells, facilitate the polarization of M1 into M2 macrophages, enhance the migration of macrophages and increase the PD-1/PD-L1/CTLA4 expression. Collectively, our well-constructed prognostic signature with GT-lncRNAs had the ability to identify two subtypes with different survival state and responses to immune therapy, which will provide reliable tools for predicting BC outcomes and making rational follow-up strategies.

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“…Panagiotis et al 34 revealed that upregulated TGF‐β/Smad‐mediated transcription and TGF‐β‐target genes resulting in the depleting of TGFB2‐AS1. Liu et al 35 observed that TGFB2‐AS1 depletion expression also prevents HepG2 cell proliferation and migration and induces apoptosis. This six immune lncRNA risk signature was powerfully correlated with the overall survival of smoking‐related LUAD patients and could also predict 1‐year, 3‐year, and 5‐year overall survival in both discovery, validation, and combine cohorts.…”

Section: Discussionmentioning

confidence: 99%

“…Ling et al33 indicated that TGFB2-AS1 regulates lung adenocarcinoma progression via mediate mir-340-5p expression to target EDNRB expression. Panagiotis et al34 revealed that upregulated TGFβ/Smad-mediated transcription and TGFβ-target genes resulting in the depleting of TGFB2-AS1.Liu et al35 observed that TGFB2-AS1 depletion expression alsoF I G U R E1 0 Expression levels of the differentially expressed genes in smoking-associated lung adenocarcinoma (LUAD) to normal tissues. (A) lncRNA.…”

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confidence: 99%

Development of six immune‐related lncRNA signature prognostic model for smoking‐positive lung adenocarcinoma

Zhou

Wang

Liu

2022

Clinical Laboratory Analysis

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Background Smoking is one of the most hazardous risk factors for the development of lung adenocarcinoma (LUAD). Many survival and prognosis‐related biomarkers were discovered using database mining. However, the precision of immune‐related long noncoding RNAs (lncRNAs) predictions is insufficient. We identified a novel signature to improve the estimate of smoking‐related LUAD prognosis. Methods The Cancer Genome Atlas database (TCGA) was used to obtain the LUAD lncRNA expression profiles. The smoking‐related LUAD cohort was randomly split into discovery and validation cohorts. To determine the risk score, use the LASSO Cox regression technique on the prognostic immune‐related lncRNA. The risk signature has been developed. Results A total of 643 immune‐related lncRNAs were identified as potential candidates for a risk signature. Finally, six immune‐related lncRNAs (AL359915.2, AP000695.1, HSPC324, TGFB2‐AS1, AC026355.1, and AC002128.2) were identified and used to carry out risk signature, which showed a close association with overall survival in the discovery cohort. We classified patients as high risk or low risk based on a median risk score of 1.0783. In the discovery cohort, overall survival was marginally longer in the low‐risk group than in the high‐risk category ( p = 2.28e08). The area under the curves (AUC) for 1‐, 3‐, and 5‐year survival was 0.67, 0.7, and 0.82, respectively. Furthermore, we successfully validated and combined cohorts using this risk profile. We discovered a strong positive connection between HSPC324 and VIPR1 as a possible novel biomarker for smoking‐related LUAD development in our study. Conclusions Our research has established a six immune‐lncRNA signature that may be used to predict the prognosis of smoking‐related LUAD with great accuracy.

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Down-regulation expression of TGFB2-AS1 inhibits the proliferation, migration, invasion and induces apoptosis in HepG2 cells

Cited by 7 publications

References 20 publications

TGFB2-AS1 binding to MED1 promotes doxorubicin-induced cardiomyocyte apoptosis via BMP7 pathway

TGFB2-AS1 binding to MED1 promotes doxorubicin-induced cardiomyocyte apoptosis via BMP7 pathway

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Development of six immune‐related lncRNA signature prognostic model for smoking‐positive lung adenocarcinoma

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