The long non-coding RNA GAS5 differentially regulates cell cycle arrest and apoptosis through activation of BRCA1 and p53 in human neuroblastoma

Mazar, Joseph; Rosado, Amy; Shelley, John; Marchica, John; Westmoreland, Tamarah

doi:10.18632/oncotarget.14244

Cited by 59 publications

(42 citation statements)

References 47 publications

(63 reference statements)

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“…GAS5 has been identified as a tumor suppressor, and its down‐regulation is related to both clinicopathological characteristics and patient prognosis in multiple cancers [Liu et al, ; Ma et al, ]. GAS5 suppresses tumorigenesis by down‐regulating miR‐23a expression in non‐small‐cell lung cancer [Mei et al, ] and gastric cancer [Liu et al, ], and it modulates cell cycle arrest and apoptosis through activation of BRCA1 and p53 in human neuroblastoma [Mazar et al, ]. GAS5 also exerts a tumor‐suppressive function by down‐regulating miR‐222 in human glioma [Zhao et al, ], and it acts as a molecular sponge to regulate miR‐103 and mediate the AKT/mTOR signaling pathway in prostate cancer [Xue et al, ] and PTEN expression in endometrial cancer [Guo et al, ].…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial–Mesenchymal Transition in Osteosarcoma by Regulating the miR‐221/ARHI Pathway

Wang

Zhang

et al. 2017

J of Cellular Biochemistry

116

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Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the roles of GAS5 and its related miRNAs in osteosarcoma are poorly understood. This study explored the potential functions and mechanisms of GAS5 in the tumorigenesis of osteosarcoma. Here, the expression of GAS5, miR-221 and aplasia Ras homologue member I (ARHI) was determined in osteosarcoma tissues and cells by Real-time PCR (RT-qPCR). The underlying mechanism of GAS5 in osteosarcoma growth was analyzed via MTT, Transwell, RT-qPCR, Western blot, dual-luciferase reporter assay, RNA immunoprecipitation, and xenograft models after GAS5 overexpression. GAS5 and ARHI levels were significantly reduced, while miR-221 increased, both in osteosarcoma tissues and cells. Overexpression of GAS5 suppressed the proliferation, migration, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. GAS5 could directly bind to miR-221 to decrease miR-221 expression and enhance ARHI expression. The effect of GAS5 overexpression on the proliferation, migration and EMT was reversed by miR-221 mimics or ARHI siRNA in osteosarcoma cells. Additionally, GAS5 suppressed tumor volume, Ki-67 and PCNA staining, and EMT process in the development of osteosarcoma in vivo. Taken together, lncRNA GAS5 functions as a competing endogenous RNA for miR-221 to suppress cell growth and EMT in osteosarcoma by regulating the miR-221/ARHI pathway. J. Cell. Biochem. 118: 4772-4781, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial–Mesenchymal Transition in Osteosarcoma by Regulating the miR‐221/ARHI Pathway

Wang

Zhang

et al. 2017

J of Cellular Biochemistry

116

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“…It has been proved that GAS5 could induce G0/G1 arrest in human neuroblastoma (Mazar, Rosado, Shelley, Marchica, & Westmoreland, ), colorectal cancer (Yang et al, ), and stomach cancer (Liu et al, ). In this study, we found that the percentage of cells in the G0/G1 phase was increased by GAS5 overexpression, but decreased by GAS5 silence, which is consistent with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Growth arrest‐specific 5 attenuates cisplatin‐induced apoptosis in cervical cancer by regulating STAT3 signaling via miR‐21

Yao

Zhang

et al. 2018

Journal Cellular Physiology

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Cervical cancer is the most common cause of female cancer‐related mortality worldwide. Decreased expression of long noncoding RNA growth arrest‐specific 5 (GAS5) is found in human cervical cancer tissues and associated with poor prognosis. However, the studies on associations between GAS5 level and malignant phenotypes, as well as sensitivity to chemotherapeutic drug in cervical cancer cells are limited. In this study, overexpression of GAS5 in cervical cancer cells resulted in prohibited cell proliferation and colony formation, which were promoted by siGAS5. Enhanced GAS5 increased cell percentage in the G0/G1 phase and decreased cells percentage in the S phase, whereas reduced expression did not. The malignant behaviors of cervical cancer cells, manifested by cell migration and invasion, could be weakened by the GAS5 overexpression and enhanced by siGAS5. Furthermore, in cisplatin‐induced cell, overexpression of GAS5 reduced cells viability and enhanced apoptosis, whereas in cells transfected with siGAS5, apoptosis eliminated. We have reported the upregulation of microRNA‐21 (miR‐21) and its oncogenetic roles in cervical cancer previously. In this study, we found the negative relationship between the GAS5 and miR‐21. Moreover, the decrease of miR‐21 associated proteins phosphorylated STAT3 and E2F3 was seen in GAS5 overexpressed cells, both of which could be increased by siGAS5. The GAS5 deficiency also reduced miR‐21 target proteins TIMP3 and PDCD4 expressions. Taken together, the GAS5 expression level is inversely associated with malignancy, but positively associated with sensitivity to cisplatin‐induced apoptosis, suggesting that GAS5 could be a biomarker of cisplatin‐resistance in clinical therapy of human cervical cancer.

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“…(growth arrest-specific 5) lncRNA acts as a tumor suppressor with various proposed mechanisms of action, including, cell cycle control Mazar et al 2016;Luo et al 2017), proliferation (Kino et al 2010;Li et al 2017b) and regulation of epithelial to mesenchymal transition (EMT) program (Zhuang et al 2015). Considering the multi-faceted mechanisms by which GAS5 functions as a tumor suppressor, it is plausible that its expression may be predictive of response to multiple drugs.…”

Section: Discussionmentioning

confidence: 99%

Discovering novel long non-coding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

Nath

Lau

Lee

et al. 2019

Preprint

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Large-scale cancer cell line screens have identified thousands of protein-coding genes (PCGs) as biomarkers of anticancer drug response. However, systematic evaluation of long non-coding RNAs (lncRNAs) as pharmacogenomic biomarkers has so far proven challenging. Here, we study the contribution of lncRNAs as drug response predictors beyond spurious associations driven by correlations with proximal PCGs, tissue-lineage or established biomarkers. We show that, as a whole, the lncRNA transcriptome is equally potent as the PCG transcriptome at predicting response to hundreds of anticancer drugs. Analysis of individual lncRNAs transcripts associated with drug response reveals nearly half of the significant associations are in fact attributable to proximal cis-PCGs. However, adjusting for effects of cis-PCGs revealed significant lncRNAs that augment drug response predictions for most drugs, including those with well-established clinical biomarkers. In addition, we identify lncRNA-specific somatic alterations associated with drug response by adopting a statistical approach to determine lncRNAs carrying somatic mutations that undergo positive selection in cancer cells. Lastly, we experimentally demonstrate that two novel lncRNA, EGFR-AS1 and MIR205HG, are functionally relevant predictors of anti-EGFR drug response.3

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The long non-coding RNA GAS5 differentially regulates cell cycle arrest and apoptosis through activation of BRCA1 and p53 in human neuroblastoma

Cited by 59 publications

References 47 publications

Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial–Mesenchymal Transition in Osteosarcoma by Regulating the miR‐221/ARHI Pathway

Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial–Mesenchymal Transition in Osteosarcoma by Regulating the miR‐221/ARHI Pathway

Growth arrest‐specific 5 attenuates cisplatin‐induced apoptosis in cervical cancer by regulating STAT3 signaling via miR‐21

Discovering novel long non-coding RNA predictors of anticancer drug sensitivity beyond protein-coding genes

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