p53-Dependent Activation of microRNA-34a in Response to Etoposide-Induced DNA Damage in Osteosarcoma Cell Lines Not Impaired by Dominant Negative p53 Expression

Novello, Chiara; Pazzaglia, Laura; Conti, Amalia; Quattrini, Irene; Pollino, Serena; Perego, Paola; Picci, Piero; Benassi, Maria Serena

doi:10.1371/journal.pone.0114757

Cited by 35 publications

(21 citation statements)

References 33 publications

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“…For example, miR-141 is reported to enhance cisplatin resistance through repression of KEAP1 in ovarian cancer cells, 6 miR-106a induces multi-drug resistance in gastric cancer by targeting RUNX3. 7 In contrast, MiR-200b and miR-15b reverse chemotherapy-induced EMT in human tongue cancer cells by targeting BMI1. 8 The involvement of miRNAs in drug resistance is just beginning to emerge, and more studies are needed to identify other miRNAs, their molecular targets and the processes they affect.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma

Tian

Wang

2015

Cancer Gene Ther

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To investigate the biological significance of abundant microRNA-23a (miR-23a) expression in osteosarcoma and its correlation with PTEN in the pathogenesis of osteosarcoma migration and invasion. The human osteosarcoma cell lines MG63, HOS58 and SaoS-2, and the human normal osteoblasts (hFOB1.19) were grown in RPMI 1640 medium supplemented with 10% fetal bovine serum. Gene and protein levels of miR-23a and PTEN were examined to determine the molecular relationship between them in the pathogenesis of osteosarcoma. Inhibition of miR-23a effectively reduced migration and invasion of osteosarcoma cell lines. Bioinformatics and luciferase-reporter assay revealed that miR-23a specifically targeted the 3'-untranslational region of PTEN and regulated its expression. Downregulation of PTEN enhanced migration and invasion of osteosarcoma cell lines. Furthermore, in tumor tissues obtained from osteosarcoma patients, the expression of miR-23a was negatively correlated with PTEN and the high expression of miR-23a combined with low expression of PTEN might serve as a risk factor for cancer patients. Besides, miR-23a-mediated suppression of PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in osteosarcoma cells, and finally enhanced the activity of osteosarcoma cell proliferation and movement and promoted osteosarcoma xenograft tumor growth in mouse models. Our study showed that miR-23a, by downregulation of PTEN, enhanced migration and invasion in osteosarcoma cells.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma

Tian

Wang

2015

Cancer Gene Ther

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“…Also, in the field of osteosarcoma research, there are much more recent research confirmed that mir-34a can inhibit cell proliferation and promotes apoptosis in human osteosarcoma cells in vitro and in vivo. [21][22][23][24][25][26][27] So, we are valid to consider that mir-34a could inhibit cell proliferation and promotes apoptosis in osteosarcoma possibly. And our results strongly suggest that miR-34a was downregulated in osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a inhibits tumor invasion and metastasis in osteosarcoma partly by effecting C-IAP2 and Bcl-2

et al. 2017

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Osteosarcoma is a common primary malignant bone tumor that occurs mainly in children and adolescents. Recent evidence has demonstrated that miR-34a is involved in the invasion and metastasis of osteosarcoma. This study aims to explore the effect of biological behavior of miR-34a on osteosarcoma. First, we collect osteosarcoma and adjacent specimens, and the relative expression of miR-34a and C-IAP2 messenger RNA was quantitated by real-time polymerase chain reaction. Furthermore, miR-34a stimulant is synthesized and transfected onto osteosarcoma MG-63 cells. The effect of overexpression of miR-34a on osteosarcoma was detected by colony-forming assay, Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I, Transwell assay, and animal experiment in vivo. Finally, the relative levels of C-IAP2 and Bcl-2 protein were checked by western blot, and the activity of caspase-3 and caspase-9 was tested by spectrophotometry assay. In conclusion, miR-34a was downregulated in osteosarcoma cells. And the expression of C-IAP2 and Bcl-2 protein was drastically inhibited, and the activities of caspase-3 and caspase-9 were significantly increased after transfecting miR-34a onto osteosarcoma MG-63 cells. And the overexpression of miR-34a can inhibit cell invasion and metastasis, promote cell apoptosis, and arrest cells in G0/G1 period. And the animal experiment in vivo demonstrated that the overexpression of miR-34a could significantly inhibit the growth of osteosarcoma in animal skin. Taken together, we indicated that miR-34a can inhibit tumor invasion and metastasis in osteosarcoma, and its mechanism may be partly related to downregulating the expression of C-IAP2 and Bcl-2 protein directly or indirectly.

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“…Furthermore, restoration of miR-34a function in OS cells using synthetic miR-34a mimics reduces cell proliferation in intro , and forced expression of miR-34a in OS cells not only inhibits cell proliferation in vitro but also represses tumorigenesis in vivo [26-29]. Nevertheless, there is no report thus far on the utility of systemic administration of a miR-34a agent or combination of miR-34a and chemotherapeutic drug for the treatment of OS in a whole body system.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth

Zhao

et al. 2015

Biochemical Pharmacology

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Osteosarcoma (OS) is the most common form of primary malignant bone tumor and prevalent among children and young adults. Recently we have established a novel approach to bioengineering large quantity of microRNA-34a (miR-34a) prodrug for miRNA replacement therapy. This study is to evaluate combination treatment with miR-34a prodrug and doxorubicin, which may synergistically suppress human OS cell growth via RNA interference and DNA intercalation. Synergistic effects were indeed obvious between miR-34a prodrug and doxorubicin for the suppression of OS cell proliferation, as defined by Chou-Talalay method. The strongest antiproliferative synergism was achieved when both agents were administered simultaneously to the cells at early stage, which was associated with much greater degrees of late apoptosis, necrosis, and G2 cell cycle arrest. Alteration of OS cellular processes and invasion capacity was linked to the reduction of protein levels of miR-34a targeted (proto-)oncogenes including SIRT1, c-MET, and CDK6. Moreover, orthotopic OS xenograft tumor growth was repressed to a significantly greater degree in mouse models when miR-34a prodrug and doxorubicin were co-administered intravenously. In addition, multiple doses of miR-34a prodrug and doxorubicin had no or minimal effects on mouse blood chemistry profiles. The results demonstrate that combination of doxorubicin chemotherapy and miR-34a replacement therapy produces synergistic antiproliferative effects and it is more effective than monotherapy in suppressing OS xenograft tumor growth. These findings support the development of mechanism-based combination therapy to combat OS and bioengineered miR-34a prodrug represents a new natural miRNA agent.

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p53-Dependent Activation of microRNA-34a in Response to Etoposide-Induced DNA Damage in Osteosarcoma Cell Lines Not Impaired by Dominant Negative p53 Expression

Cited by 35 publications

References 33 publications

RETRACTED ARTICLE: MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma

RETRACTED ARTICLE: MicroRNA-23a enhances migration and invasion through PTEN in osteosarcoma

MicroRNA-34a inhibits tumor invasion and metastasis in osteosarcoma partly by effecting C-IAP2 and Bcl-2

Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth

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