scholarly journals MiR-122 Promotes the Development of Colon Cancer by Targeting ALDOA In Vitro

2019 ◽  
Vol 18 ◽  
pp. 153303381987130 ◽  
Author(s):  
Hong Li ◽  
Xinhua Zhang ◽  
Zhao Jin ◽  
Tao Yin ◽  
Chuanyi Duan ◽  
...  

Non-coding RNAs, originally considered junk gene products, have taken center stage in view of their significant involvement in a spectrum of biological processes during human development, thereby offering novel therapeutic targets for improvement of treatment options. Accumulating evidence has demonstrated non-coding RNA dysfunction across various human cancers. In particular, microRNAs have emerged as key regulatory molecules in cancer biology. MicroRNAs are noninvasive, readily accessible biomarkers that can be effectively applied for diagnosis and prognosis of different tumor types, including colon cancer. In this study, we reanalyzed the available data with bioinformatics tools to identify differentially expressed microRNAs in colon cancer cells. The top 3 upregulated microRNAs (miR-10, miR-199, and miR-122) in colon cancer cells were further validated in tissues of clinical patients via reverse transcription-quantitative polymerase chain reaction. Our results showed that miR-122 significantly promotes the proliferation and invasion ability of SW480 and SW620 cells through inhibition of Aldolase, Fructose-Bisphosphate A ( ALDOA) expression. We further summarized recent advances in our understanding of the functional relevance of microRNAs in cancer development and discussed the possible implications of specific microRNAs in colon cancer. This study extends our knowledge of microRNA involvement in colon cancer biology and presents novel candidates for the development of attractive therapeutic strategies.

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Yanwei Luo ◽  
Fengxia Liu ◽  
Jinqi Ma ◽  
Yunfeng Fu ◽  
Rong Gui

Abstract Foxp1 is a tumor suppressor in colon cancer. However, circFoxp1 derived from Foxp1 is an oncogene. In this study, we aim to investigate the role of circFoxp1 in colon cancer and the regulatory mechanism between circFoxp1 and Foxp1. 78 human colon tumor tissues and the matched paracancerous tissues were collected. Quantitative polymerase chain reaction, immunohistochemistry, quantitative methylation-specific PCR, chromatin immunoprecipitation assay, CCK-8 assay, and Tumor xenograft in nude mice were performed. The expression of circFoxp1 was increased and Foxp1 was reduced in colon cancer tissues, which were associated with a poor overall survival rate of the patients with colon cancer. CircFoxp1 recruited DNMT1 to the promoter of Foxp1, leading to promotor hypermethylation, thereby inhibiting Foxp1 transcription. Interfering circFoxp1 by siRNA in SW620 cells significantly inhibited cell viability, while knockdown Foxp1 expression partially restored SW620 cell viability. In addition, knockdown of circFoxp1 significantly sensitized colon cancer cells to Capecitabine in vitro and vivo through regulating Foxp1. We discovered a novel epigenetic pathway that circFoxp1 regulated Foxp1 in colon cancer cells. CircFoxp1 may regulate DNA methylation and demethylation to coordinate colon cancer cell proliferation and participate in chemotherapy drug responses. Therefore, circFoxp1 may be a potential therapeutic target for colon cancer.


2020 ◽  
Vol 19 ◽  
pp. 153473542097247
Author(s):  
Xue-Cong Zheng ◽  
Ze-Sheng Shi ◽  
Cheng-Zhi Qiu ◽  
Zhong-Shi Hong ◽  
Chun-Xiao Wang ◽  
...  

Protosappanin B (PSB) is a key active component of Lignum Sappan extract. Although the antiproliferative effects of Lignum Sappan extract have been demonstrated in various cancer cells, relatively little is known about the effects of PSB on tumor progression. The aim of this study was to explore the anti-tumor effects of PSB on human colon cancer cells by regulation of intracellular signaling pathways and Golgi phosphoprotein 3 (GOLPH3) expression in vitro and in vivo. Our results showed that PSB effectively inhibited the viability and migration of SW620 cells and induced apoptosis, but had poor effect on HCT116 cells. Furthermore, PSB significantly reduced the expression of p-AKT, p-p70S6K, β-catenin, and p-ERK1/2 proteins in SW620 cells, and this effect was reversed by the corresponding signaling pathway agonists. Interestingly, PSB could also suppress GOLPH3 expression of SW620 cells in a concentration-dependent manner, but SW620 cells transfected with lentiviral vectors overexpressing GOLPH3 can effectively resist the cytotoxic activity of PSB in vitro. The xenograft experiment of SW620 cells with LV-GOLPH3 confirmed that PSB distinctly inhibited the tumor growth via suppressing GOLPH3 expression. Collectively, these findings clarified a new anti-cancer mechanism of PSB through inhibition of GOLPH3 expression and intracellular signaling pathways in colon cancer cells. PSB may be a potential new drug for colon cancer.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
James Evans ◽  
Anthony Essex ◽  
Hong Xin ◽  
Nurith Amitai ◽  
Lindsey Brinton ◽  
...  

The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by replicating selected results from a substantial number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (<xref ref-type="bibr" rid="bib5">Errington et al., 2014</xref>). This Registered report describes the proposed replication plan of key experiments from ‘Wnt activity defines colon cancer stem cells and is regulated by the microenvironment’ by Vermeulen and colleagues, published in Nature Cell Biology in 2010 (<xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). The key experiments that will be replicated are those reported in Figures 2F, 6D, and 7E. In these experiments, Vermeulen and colleagues utilize a reporter for Wnt activity and show that colon cancer cells with high levels of Wnt activity also express cancer stem cell markers (Figure 2F; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). Additionally, treatment either with conditioned medium derived from myofibroblasts or with hepatocyte growth factor restored clonogenic potential in low Wnt activity colon cancer cells in vitro (Figure 6D; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>) and in vivo (Figure 7E; <xref ref-type="bibr" rid="bib20">Vermeulen et al., 2010</xref>). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.


Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.


Author(s):  
Mattias Lepsenyi ◽  
Nader Algethami ◽  
Amr A. Al-Haidari ◽  
Anwar Algaber ◽  
Ingvar Syk ◽  
...  

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.


2021 ◽  
Vol 10 (1) ◽  
pp. 572-585
Author(s):  
Darren Yi Sern Low ◽  
Camille Keisha Mahendra ◽  
Janarthanan Supramaniam ◽  
Loh Teng Hern Tan ◽  
Learn Han Lee ◽  
...  

Abstract In this study, ultrasonically driven biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Swietenia macrophylla seed ethyl acetate fraction (SMEAF) has been reported. X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses confirmed the presence of a pure hexagonal wurtzite structure of ZnO. Field emission scanning electron microscope images revealed the formation of uniquely identifiable uniform rice-shaped biologically synthesized ZnOSMEAF particles. The particle sizes of the biosynthesized NPs ranged from 262 to 311 nm. The underlying mechanisms for the biosynthesis of ZnOSMEAF under ultrasound have been proposed based on FTIR and XRD results. The anticancer activity of the as-prepared ZnOSMEAF was investigated against HCT-116 human colon cancer cell lines via methyl thiazolyl tetrazolium assay. ZnOSMEAF exhibited significant anticancer activity against colon cancer cells with higher potency than ZnO particles prepared using the chemical method and SMEAF alone. Exposure of HCT-116 colon cancer cells to ZnOSMEAF promoted a remarkable reduction in cell viability in all the tested concentrations. This study suggests that green sonochemically induced ZnO NPs using medicinal plant extract could be a potential anticancer agent for biomedical applications.


2012 ◽  
Vol 23 ◽  
pp. iv85-iv86
Author(s):  
Ying Lin ◽  
Yuan-yuan Fang ◽  
Hong Su ◽  
Zhou Hui-Min ◽  
Qi-Kui Chen

2016 ◽  
Vol 65 (31) ◽  
pp. 6477-6487 ◽  
Author(s):  
María-Carmen López de las Hazas ◽  
Juana I. Mosele ◽  
Alba Macià ◽  
Iziar A. Ludwig ◽  
María-José Motilva

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