Aplasia Ras homologue member I overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture

Ye, Kaishan; Wang, Shuanke; Yong, Yang; Kang, Xuewen; Wang, Jing; Han, Hua

doi:10.3892/ijmm.2015.2278

Cited by 10 publications

(11 citation statements)

References 33 publications

(39 reference statements)

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“…Therefore, we considered that the downregulation of ARHI expression is mainly caused by hypermethylation of the ARHI promotor region, leading to loss of the ability to suppress cell survival in osteosarcoma cells. A recent study clarified the inhibitory role of ARHI in growth and its role in promoting apoptosis in osteosarcoma cells . We did not repeat showing the role of ARHI in cell viability and apoptosis in this study.…”

Section: Discussionmentioning

confidence: 54%

“…A recent study clarified the inhibitory role of ARHI in growth and its role in promoting apoptosis in osteosarcoma cells. (19) We did not repeat showing the role of ARHI in cell viability and apoptosis in this study. However, we showed that knockdown of ARHI rescues cell viability and apoptosis following zebularine treatment, supporting the proposition that ARHI could inhibit osteosarcoma growth and induce apoptosis.…”

Section: Discussionmentioning

confidence: 70%

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Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI

Wang

et al. 2016

Cancer Science

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ARHI is an imprinted tumor suppressor gene and its methylation suppresses ARHI transcription levels to cause the development and progression of malignant tumors. Zebularine exerts a demethylation function for tumor suppressor genes. Our study aims to investigate the effect and mechanism of action of zebularine on the epigenetic modification of the ARHI gene, and whether this effect may modulate the viability and apoptosis of human osteosarcoma cells. We found that zebularine inhibited the viability and promoted apoptosis in osteosarcoma cells. Zebularine potentiated the expression of ARHI at both the protein and mRNA level. This was related to the downregulation of methylation of ARHI caused by zebularine. Zebularine suppressed the interaction of DNA methyltransferase 1 (DNMT1) with histone methyltransferase G9a, but had no effect on G9a alone. Knockdown of DNMT1 or G9a can induce a reduction of ARHI methylation. Therefore, we inferred that zebularine was likely to directly repress DNMT1 alone, but G9a was necessary to regulate the function of DNMT1 on ARHI methylation. Moreover, knockdown of ARHI rescued cell viability and apoptosis under the zebularine‐treated condition. We showed that zebularine inhibited viability and promoted apoptosis by disturbing the interaction between DNMT1 and G9a, thereby resulting in lower ARHI methylation and elevated ARHI expression in osteosarcoma cells.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 70%

Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI

Wang

et al. 2016

Cancer Science

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“…Previous studies have reported that miR-221 promotes tumor development, while ARHI is a tumor suppressor gene [Chen et al, 2011;Li et al, 2013b;Ye et al, 2015Ye et al, , 2016. We transfected miR-221 mimics and si-ARHI into GAS5-overexpressing MG-63 cells to investigate the role of miR-221 and ARHI on cell proliferation, migration, and EMT of osteosarcoma cells.…”

Section: Gas5 Suppresses Cell Proliferation Migration and Emt Via Regulating Mir-221 And Arhi Expression In Osteosarcoma Cellsmentioning

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

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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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“…Caspase3 plays an irreplaceable role in cell apoptosis. Caspase3 can be activated by a variety of factors, and it is the main terminal shear enzyme in the process of cell apoptosis 26 , 27 . Taken together, these results indicated that Tec possesses effective antitumor activities against OS through activation of caspase apoptosis axis.…”

Section: Discussionmentioning

confidence: 99%

Tectorigenin inhibits osteosarcoma cell migration through downregulation of matrix metalloproteinases in vitro

Chen

Cheng

et al. 2016

Anti-Cancer Drugs

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Tectorigenin (Tec) is an effective component of the traditional Chinese medicine Belamcanda chinensis, which has been reported to exert beneficial effects in various types of cancer. However, the activity and mechanism of Tec in osteosarcoma (OS) have not been investigated to date. The aim of the present study was to examine the inhibitory effect of Tec on OS and its underlying mechanism of action. OS cells (Saos2 and U2OS) were treated with various concentrations of Tec for 24, 48, and 72 h. Cell proliferation was evaluated using an CCK-8 assay. Cell migration and invasion ability were measured using the Transwell assay. The expressions of MMP1, MMP2, MMP9, and cleaved caspase3 were measured using real-time PCR and/or western blot analysis. We found that Tec inhibited the proliferation of OS cells (Saos2 and U2OS) in a dose-dependent and time-dependent manner. In addition, Tec significantly inhibited migration and invasion in OS cells (P<0.05). Tec upregulated the expression of cleaved caspase3, while downregulating the expression of MMP1, MMP2, and MMP9. Taken together, the present study provided fundamental evidence for the application of Tec in chemotherapy against OS.

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Aplasia Ras homologue member I overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture

Cited by 10 publications

References 33 publications

Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI

Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI

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

Tectorigenin inhibits osteosarcoma cell migration through downregulation of matrix metalloproteinases in vitro

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