miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1

Zheng, Ziming; Ding, Muliang; Ni, Jiangdong; Song, Deye; Huang, Jun; Wang, Junjie

doi:10.3892/or.2014.3687

Cited by 26 publications

(54 citation statements)

References 26 publications

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“…In this work, the overexpression of SRGAP2 also slowed cellular migration in murine osteosarcoma cell lines and the knockout of Srgap2 increased cellular migration in the K12 cell line. However, unlike what has been observed in other studies of SRGAP2, knockout of Srgap2 slowed cellular proliferation in osteosarcoma cell lines1624.…”

Section: Discussioncontrasting

confidence: 93%

“…Other modulators of Rac1 have also been implicated in osteosarcoma metastasis. Micro-RNA (miR)-142 has been shown to regulate Rac1 expression in osteosarcoma cell lines by targeting the 3’-untranslated region of the SRGAP2 transcript and blocking translation of the protein24. Expression of miR-142 or direct silencing of Rac1 inhibited cellular invasion as well as cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

Marko

Shamsan

Edwards

et al. 2016

Sci Rep

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Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2. Proliferation, migration, and anchorage independent growth were evaluated. RNA sequencing and immunohistochemistry of human osteosarcoma tissue samples were used to further evaluate the potential role of the Slit-Robo pathway in osteosarcoma. The effects of Srgap2 expression modulation in the murine OS cell lines support the hypothesis that SRGAP2 may have a role as a suppressor of metastases in osteosarcoma. Additionally, SRGAP2 and other genes in the Slit-Robo pathway have altered transcript levels in a subset of mouse and human osteosarcoma, and SRGAP2 protein expression is reduced or absent in a subset of primary tumor samples. SRGAP2 and other axon guidance proteins likely play a role in osteosarcoma metastasis, with loss of SRGAP2 potentially contributing to a more aggressive phenotype.

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Section: Discussioncontrasting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

Marko

Shamsan

Edwards

et al. 2016

Sci Rep

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“…Rac1 is a GTPase that is involved in diverse physiological activities, including cell growth, migration and invasion [33]. Until now, large numbers of miRNAs are reported to act as tumor suppressors by targeting Rac1, including miR-142 and miR-146a [34, 35]. Previous studies also proved that Rac1 participates in various cardiovascular pathologies, for example, cardiomyocyte hypertrophy [36].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Wang

Zhang

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Myocardial infarction (MI) is a leading cause of morbidity and mortality. Here, we sought to explore the potential role and underlying mechanism of miR-145 in MI. Methods: H9c2 cells were cultured under persistent hypoxia to simulate MI. The hypoxia-induced injury was assessed on the basis of cell viability, migration, invasion and apoptosis. The expression of miR-145 was evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2 cells under hypoxia was also estimated. Utilizing bioinformatics methods, the target genes of miR-145 were verified by luciferase reporter assay. Then, effects of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed. Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways were detected by Western blot analysis. Results: Hypoxia remarkably lowered viability, migration and invasion but promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2 cells under hypoxia. Following experiments suggested that hypoxia-induced injury was exacerbated by miR-145 overexpression while was alleviated by miR-145 silence. Rac1 was predicted and further validated to be a target gene of miR-145. The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K, AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these alterations were reversed by down-regulation of Rac1. Conclusion: miR-145 silencing could protect H9c2 cells against hypoxia-induced injury by targeting Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

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“…Our studies showed that LDHA downregulation inhibits cell migration, invasion and tube formation. Furthermore, our data showed that depletion of LDHA decreased the expression of MMP-2 and MMP-9, suggesting that LDHA may be involved in RCC invasion through inducing enzyme-based degradation of the extracellular matrix [23,24] . Furthermore, it is worth noting that LDHA depletion with siRNA leads to diminished VEGF and VE-cadherin levels, which are known to modulate vascular angiogenesis [25] and tumor development [26,27] .…”

Section: Discussionmentioning

confidence: 86%

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

Wang

et al. 2016

Urol Int

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Purpose: Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated. Methods: MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer. Results: Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Conclusions: These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.

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miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1

Cited by 26 publications

References 26 publications

Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

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