Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiu-Hong; Zhao, Zheng

doi:10.1016/j.bbrc.2011.03.140

Cited by 52 publications

(46 citation statements)

References 31 publications

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“…We initially showed that inhibition of Fyn either by siRNA or by miR-125a-3p led to a decrease in the proliferation of HEK 293T cells and to their arrest at the G2/M phase of the cell cycle. These findings are in agreement with lines of evidence indicating the role of SFKs in cell proliferation and in the G2/M transition of the cell cycle (Zhao et al, 2011;Arai et al, 2012;Hitosugi et al, 2007) as well as with the finding that SU6656, an SFK inhibitor, induces a defective cleavage of mouse oocyte (Levi et al, 2010) and a defective cleavage furrow formation in synovial sarcoma cells, resulting in their arrest at the G2/M phase and their subsequent apoptosis (Arai et al, 2012). Furthermore, inhibition of Fyn by microinjection of dominant-negative Fyn into mouse oocytes caused inhibition of the second polar body extrusion and of the first mitotic cleavage (Levi et al, 2011;Gallo et al, 2012).…”

Section: Discussionsupporting

confidence: 93%

“…To assess the feasibility of the use of miR-125a-3p as a regulator of Fyn expression in various cancerous cells, we examined the expression of Fyn mRNA in miR-125a-3p-overexpressing cancer cell lines: MNT-1 (melanoma cancer), U2OS (osteosarcoma), MDA-MB-231, MCF-7 and SKBR3 (breast cancers), PC3 (prostate cancer) and HeLa (cervical cancer). The role of Fyn in tumor progression or its overexpression has already been illustrated in these cancer cell lines, with the exception of osteosarcoma (Teutschbein et al, 2009;Huang et al, 2003;Zhao et al, 2011;Posadas et al, 2009;Bilal et al, 2010;Yadav and Denning, 2011). We found that the expression of Fyn mRNA was reduced in all the examined cell lines, except HeLa cells (Fig.…”

Section: Mir-125a-3p Negatively Regulates the Activity Of Proteins Dosupporting

confidence: 70%

“…We focused on three regulatory Fyn downstream proteins: Akt, a regulator of cell growth and proliferation (Testa and Tsichlis, 2005), and FAK and paxillin, regulators of cell motility (Llić et al, 1995;Zhao et al, 2011;Deakin and Turner, 2008). We demonstrated that their activation was inhibited once Fyn was knocked-down either by Fyn siRNA or by overexpressing miR-125a-3p.…”

Section: Discussionmentioning

confidence: 99%

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microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

Ninio-Many

Grossman

Shomron

et al. 2013

Journal of Cell Science

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SummaryFyn, a member of the Src family kinases (SFKs), has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. MicroRNAs (miRNAs) play a major role in post-transcriptional repression of protein expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor-suppressing miRNA that is downregulated in several cancer cell types and on our bioinformatics studies presented here, we chose to examine the post-transcription regulation of Fyn by miR-125a-3p in the HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p. Following this reduction, the activity of proteins downstream of Fyn, such as FAK, paxillin and Akt (proteins known to be overexpressed in various tumors), is also reduced. On a broader level, we show that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration, probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p, as well as by the fact that numerous cancer cell lines show a significant downregulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, which implies that it has a therapeutic potential in overexpressed Fyn-related diseases.

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Section: Discussionsupporting

confidence: 93%

Section: Mir-125a-3p Negatively Regulates the Activity Of Proteins Dosupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

Ninio-Many

Grossman

Shomron

et al. 2013

Journal of Cell Science

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“…NDRG1 is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation (35,36). Studies demonstrated that NDRG1 expression was decreased in cancer primary and metastatic cells when compared to normal cells and was thought to function as a metastasis suppressor in cancer types including ovarian, colon, and prostate cancers (37)(38)(39). NDRG1 has also been reported to be necessary for p53-mediated apoptosis and it plays a role in suppressing malignant cell growth (40).…”

Section: Discussionmentioning

confidence: 99%

Chronic stress promoted the growth of ovarian carcinoma via increasing serum levels of norepinephrine and interleukin-10 and altering nm23 and NDRG1 expression in tumor tissues in nude mice

et al. 2013

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“…[22][23][24][25] Cells were cultured in Dulbecco's modified Eagle's medium (Gibco, NY, USA) supplemented with 10% fetal bovine serum (Gibco), in a humidified atmosphere containing 5% CO 2 at 37 C. Hypoxic conditions were created using a hypoxia chamber contained 1% O 2 , 5% CO 2 , and balanced with N 2 or using CoCl 2 to produce hypoxic conditions. CoCl 2 , YC-1, DiI, DAPI, and Alexa Fluor 594-labeled phalloidin were purchased from Sigma-Aldrich (St Louis, MI, USA).…”

Section: Cell Culture and Materialsmentioning

confidence: 99%

Hypoxia promotes HO-8910PM ovarian cancer cell invasion via Snail-mediated MT1-MMP upregulation

Sun

Lin

Zhuo

et al. 2015

Exp Biol Med (Maywood)

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The molecular mechanisms of ovarian cancer cell invasion under hypoxia remain unclear. Here we employed a 3D collagen model and chick chorioallantoic membrane (CAM) invasion assay to explore the influence of hypoxia on ovarian cancer cell invasion. Hypoxia (both 1% O 2 and CoCl 2 150 and 250 mM) induced HO-8910PM ovarian cancer cell invasion in 3D collagen and collagenolysis determined by hydroxyproline. Pretreatment with a hypoxia inducible factor-1a inhibitor, YC-1, or MMP inhibitor, GM6001, significantly inhibited 3D collagen invasion and degradation and cell proliferation. Hypoxia stimulated both mRNA and protein expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP) and promoted MT1-MMP translocation to the cell surface in an YC-1 sensitive manner. MT1-siRNA transfection inhibited hypoxia-induced invasion, proliferation, and collagen degradation of cells in 3D collagen. Hypoxia stimulated Snail mRNA and protein expression as well as translocation to nucleus in an YC-1 sensitive manner. Overexpression of Snail with a recombinant plasmid in HO-8910PM cells resulted in an enhanced invasion in 3D collagen. Transfection with Snail-specific siRNA significantly decreased MT1-MMP expression and 3D collagen invasion. Hypoxia-treated cells significantly broke the upper CAM surface of 11-day-old chick embryos and infiltrated interstitial tissue, completely blocked in the presence of YC-1 or GM6001, or after MT1-MMP siRNA or Snail siRNA transfection. Together, these data suggest that hypoxia promotes HO-8910PM ovarian cancer cell traffic through 3D matrix via Snail-mediated MT1-MMP upregulation, a possible molecular mechanism of ovarian cancer cell invasion under hypoxia.

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Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

Cited by 52 publications

References 31 publications

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

microRNA-125a-3p reduces cells proliferation and migration by targeting Fyn

Chronic stress promoted the growth of ovarian carcinoma via increasing serum levels of norepinephrine and interleukin-10 and altering nm23 and NDRG1 expression in tumor tissues in nude mice

Hypoxia promotes HO-8910PM ovarian cancer cell invasion via Snail-mediated MT1-MMP upregulation

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