scholarly journals miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

2018 ◽  
Vol 51 (4) ◽  
pp. 1969-1981 ◽  
Author(s):  
Xiangyu Zhu ◽  
Si-ping Ma ◽  
Dongxiang Yang ◽  
Yanlong Liu ◽  
Yong-peng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Tumor Cell ◽  
Nude Mice ◽  
Colony Formation ◽  
Tumor Cell Growth ◽  
Rt Pcr ◽  
Tumor Tissues

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.

GF-15, a Novel Inhibitor of Centrosomal Clustering, Suppresses Tumor Cell Growth In Vitro and In Vivo

2012 ◽  
Vol 72 (20) ◽  
pp. 5374-5385 ◽  
Author(s):  
Marc S. Raab ◽  
Iris Breitkreutz ◽  
Simon Anderhub ◽  
Mads H. Rønnest ◽  
Blanka Leber ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth

scholarly journals p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression

2008 ◽  
Vol 183 (4) ◽  
pp. 737-749 ◽  
Author(s):  
Edwin Soto ◽  
Masahiro Yanagisawa ◽  
Laura A. Marlow ◽  
John A. Copland ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Tumor Cell Growth ◽  
P120 Catenin ◽  
Opposing Effects ◽  
E Cadherin

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1–mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.

Abstract LB-231: An optide (optimized knottin-peptide) that inhibits tumor cell growth In vitro and accumulates in sarcoma flank tumors in vivo

2016 ◽  
Author(s):  
Theo Sottero ◽  
Emily J. Girard ◽  
Colin Correnti ◽  
Mark R. Stroud ◽  
Brandon L. Kier ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth

scholarly journals TUSC1, a Putative Tumor Suppressor Gene, Reduces Tumor Cell Growth In Vitro and Tumor Growth In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66114 ◽  
Author(s):  
Zhihong Shan ◽  
Abbas Shakoori ◽  
Sohrab Bodaghi ◽  
Paul Goldsmith ◽  
Jen Jin ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Suppressor Gene ◽  
Tumor Cell Growth ◽  
Putative Tumor Suppressor Gene ◽  
Putative Tumor Suppressor

scholarly journals Esterase D stabilizes FKBP25 to suppress mTORC1

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Yuejun Yang ◽  
Xinpeng Chen ◽  
Wen Yao ◽  
Xiaoling Cui ◽  
Na Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Nonspecific Esterase ◽  
Tumor Cell Growth ◽  
Yeast Two Hybrid ◽  
Mtorc1 Signaling ◽  
Two Hybrid

Abstract Background Esterase D (ESD) is a nonspecific esterase that detoxifies formaldehyde. Many reports have stated that ESD activity is associated with a variety of physiological and pathological processes. However, the detailed signaling pathway of ESD remains poorly understood. Methods Considering the advantages of the small chemical molecule, our recent work demonstrated that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) activates ESD, and will be a good tool for studying ESD further. Firstly, we determined the interaction between ESD and FK506 binding protein 25 (FKBP25) by yeast two-hybrid assay and co-immunoprecipitation (CO-IP) and analyzed the phosphorylation levels of mTORC1, P70S6K and 4EBP1 by western blot. Furthermore, we used the sulforhodamine B (SRB) and chick chorioallantoic membrane (CAM) assay to analyze cell viability in vitro and in vivo after treatment with ESD activator FPD5. Results We screened FKBP25 as a candidate protein to interact with ESD by yeast two-hybrid assay. Then we verified the interaction between ESD and endogenous FKBP25 or ectopically expressed GFP-FKBP25 by CO-IP. Moreover, the N-terminus (1–90 aa) domain of FKBP25 served as the crucial element for their interaction. More importantly, ESD reduced the K48-linked poly-ubiquitin chains of FKBP25 and thus stabilized cytoplasmic FKBP25. ESD also promoted FKBP25 to bind more mTORC1, suppressing the activity of mTORC1. In addition, ESD suppressed tumor cell growth in vitro and in vivo through autophagy. Conclusions These findings provide novel evidence for elucidating the molecular mechanism of ESD and ubiquitination of FKBP25 to regulate autophagy and cancer cell growth. The ESD/FKBP25/mTORC1 signaling pathway is involved in inhibiting tumor cell growth via regulating autophagy.

scholarly journals Oncogenic human herpesvirus hijacks proline metabolism for tumorigenesis

2020 ◽  
Vol 117 (14) ◽  
pp. 8083-8093 ◽  
Author(s):  
Un Yung Choi ◽  
Jae Jin Lee ◽  
Angela Park ◽  
Wei Zhu ◽  
Hye-Ra Lee ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Growth ◽  
Tumor Cell ◽  
Kaposi's Sarcoma ◽  
3D Culture ◽  
Tumor Cell Growth ◽  
Proline Metabolism ◽  
Proline Biosynthesis

Three-dimensional (3D) cell culture is well documented to regain intrinsic metabolic properties and to better mimic the in vivo situation than two-dimensional (2D) cell culture. Particularly, proline metabolism is critical for tumorigenesis since pyrroline-5-carboxylate (P5C) reductase (PYCR/P5CR) is highly expressed in various tumors and its enzymatic activity is essential for in vitro 3D tumor cell growth and in vivo tumorigenesis. PYCR converts the P5C intermediate to proline as a biosynthesis pathway, whereas proline dehydrogenase (PRODH) breaks down proline to P5C as a degradation pathway. Intriguingly, expressions of proline biosynthesisPYCRgene and proline degradationPRODHgene are up-regulated directly by c-Myc oncoprotein and p53 tumor suppressor, respectively, suggesting that the proline-P5C metabolic axis is a key checkpoint for tumor cell growth. Here, we report a metabolic reprogramming of 3D tumor cell growth by oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV), an etiological agent of Kaposi’s sarcoma and primary effusion lymphoma. Metabolomic analyses revealed that KSHV infection increased nonessential amino acid metabolites, specifically proline, in 3D culture, not in 2D culture. Strikingly, the KSHV K1 oncoprotein interacted with and activated PYCR enzyme, increasing intracellular proline concentration. Consequently, the K1-PYCR interaction promoted tumor cell growth in 3D spheroid culture and tumorigenesis in nude mice. In contrast, depletion ofPYCRexpression markedly abrogated K1-induced tumor cell growth in 3D culture, not in 2D culture. This study demonstrates that an increase of proline biosynthesis induced by K1-PYCR interaction is critical for KSHV-mediated transformation in in vitro 3D culture condition and in vivo tumorigenesis.

scholarly journals LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2995
Author(s):  
Yuan Li ◽  
Shumei Song ◽  
Melissa Pool Pizzi ◽  
Guangchun Han ◽  
Ailing W. Scott ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Gastric Adenocarcinoma ◽  
Poor Prognosis ◽  
Survival Duration ◽  
Tumor Cell Growth ◽  
Normal Tissues ◽  
Antisense Oligos

Gastric adenocarcinoma (GAC) is inherently resistant or becomes resistant to therapy, leading to a poor prognosis. Mounting evidence suggests that lncRNAs can be used as predictive markers and therapeutic targets in the right context. In this study, we determined the role of lncRNA-PVT1 in GAC along with the value of inhibition of PVT1 using antisense oligos (ASOs). RNA scope in situ hybridization was used to analyze PVT1 expression in tumor tissue microarrays (TMAs) of GAC and paired normal tissues from 792 patients. Functional experiments, including colony formation and invasion assays, were performed to evaluate the effects of PVT1 ASO inhibition of PVT1 in vitro; patient-derived xenograft models were used to evaluate the anti-tumor effects of PVT1 ASOs in vivo. LncRNA-PVT1 was upregulated in GACs compared to the matched adjacent normal tissues in the TMA. LncRNA PVT1 expression was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration. Inhibition of PVT1 using PVT1 ASOs significantly suppressed tumor cell growth and invasion in vitro and in vivo. PVT1 expression was highly associated with poor prognosis in GAC patients and targeting PVT1 using PVT1 ASOs was effective at curtailing tumor cell growth in vitro and in vivo. Thus, PVT1 is a poor prognosticator as well as therapeutic target. Targeting PVT1 using PVT1 ASOs provides a novel therapeutic strategy for GAC.

scholarly journals In Vitro and In Vivo Inhibition of Neuroblastoma Tumor Cell Growth by AKT Inhibitor Perifosine

2010 ◽  
Vol 102 (11) ◽  
pp. 758-770 ◽  
Author(s):  
Z. Li ◽  
F. Tan ◽  
D. J. Liewehr ◽  
S. M. Steinberg ◽  
C. J. Thiele
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Akt Inhibitor ◽  
Neuroblastoma Tumor
Sign in / Sign up

Export Citation Format

Share Document