scholarly journals 4-[6-(4-Isopropoxyphenyl)Pyrazolo[1,5-a]Pyrimidin-3-yl]Quinoline) Suppresses Metastasis Through HIF-1α/MCT-4-Mediated Lactate Excretion in Colorectal Cancer Cells

2021 ◽  
Author(s):  
Chang chen ◽  
Xue Tan ◽  
Xiaotong Kou ◽  
Xiaoling Qin ◽  
Zhongsha Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Intracellular Ph ◽  
Cancer Metastasis ◽  
Inhibitory Effect ◽  
Morphogenetic Protein ◽  
Colorectal Cancer Metastasis ◽  
Lactate Excretion

Abstract DMH1 (D4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) is a bone morphogenetic protein antagonist. However, the influence of DMH1 on colorectal cancer metastasis remains unknown. Hence, This study aimed to investigate the inhibitory effect of DMH1 on the migration of cancer cells. In vitro incubation with DMH1(1mM) inhibited the high protein level of HIF-1α in CT-26 cells. Transwell assay confirmed that DMH1 suppress CT-26 cells migration via the HIF-1α under hypoxia. The accumulation of lactate in culture medium down-regulated the extracellular pH, then stimulated the migration of CT-26 cells. DMH1 suppressed the migration of CT-26 cells through HIF-1α/MCT-4 signaling pathway mediate the excreation of lactate. The data demonstrated that DMH1 downregulated the high intracellular pH levels via the HIF-1α/MCT-4 signaling pathway to mediate lactate excretion. This study indicated that DMH1 might serve as a potential drug for treating tumor migration by minimizing the intracellular pH via the HIF-1α/MCT-4 signaling pathway.

scholarly journals MicroRNA-124 Regulates the Proliferation of Colorectal Cancer Cells by TargetingiASPP

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Kuijie Liu ◽  
Hua Zhao ◽  
Hongliang Yao ◽  
Sanlin Lei ◽  
Zhendong Lei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Prediction ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Small Noncoding Rnas ◽  
Colorectal Cancer Cells ◽  
Microrna 124

MicroRNAs are a class of small, noncoding RNAs that function as critical regulators of gene expression by targeting mRNAs for translational repression or degradation. In this study, we demonstrate that expression of microRNA-124 (miR-124) is significantly downregulated in colorectal cancer tissues and cell lines, compared to the matched adjacent tissues. We identified and confirmed inhibitor of apoptosis-stimulating protein of p53 (iASPP) as a novel, direct target of miR-124 using target prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed iASPP protein expression, upregulated expression of the downstream signaling molecule nuclear factor-kappa B (NF-κB), and attenuated cell viability, proliferation, and colony formation in SW480 and HT-29 colorectal cancer cells in vitro. Forced overexpression ofiASPPpartly rescued the inhibitory effect of miR-124 on SW480 and HT29 cell proliferation. Taken together, these findings shed light on the role and mechanism of action of miR-124, indicate that the miR-124/iASPP axis can regulate the proliferation of colorectal cancer cells, and suggest that miR-124 may serve as a potential therapeutic target for colorectal cancer.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

scholarly journals Novel proapoptotic agent SM-1 enhances the inhibitory effect of 5-fluorouracil on colorectal cancer cells in vitro and in vivo

2017 ◽  
Vol 13 (6) ◽  
pp. 4762-4768 ◽  
Author(s):  
Ying Wang ◽  
Shoujun Yuan ◽  
Linna Li ◽  
Dexuan Yang ◽  
Chengwang Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Colorectal Cancer Cells

scholarly journals Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of In Vitro Studies

2016 ◽  
Vol 15s4 ◽  
pp. CIN.S40301
Author(s):  
Nguyen Phuoc Long ◽  
Wun Jun Lee ◽  
Nguyen Truong Huy ◽  
Seul Ji Lee ◽  
Jeong Hill Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microarray Data ◽  
Cancer Metastasis ◽  
Meta Analysis ◽  
Data Sets ◽  
Proteomic Data ◽  
Colorectal Cancer Metastasis ◽  
Microarray Studies ◽  
Potential Biomarkers

Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes. Of these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I also have potential. Other candidates were more controversial, possibly because of the biologic heterogeneity of tumor cells, which is a major obstacle to predicting metastasis. In conclusion, we demonstrated a meta-analysis approach and successfully suggested ten biomarker candidates for future investigation.

scholarly journals Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinbing Sun ◽  
Zhihua Lu ◽  
Wei Fu ◽  
Kuangyi Lu ◽  
Xiuwen Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Niche ◽  
Colorectal Cancer Cells ◽  
Niche Formation ◽  
Underlying Mechanisms

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

scholarly journals PLAGL2 promotes epithelial–mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

2019 ◽  
Vol 122 (4) ◽  
pp. 578-589
Author(s):  
Liang Wu ◽  
Zili Zhou ◽  
Shengbo Han ◽  
Jinhuang Chen ◽  
Zhengyi Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumours ◽  
Mesenchymal Transition ◽  
Exact Function ◽  
Colorectal Cancer Metastasis

Abstract Background We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal cancer (CRC) remain largely unknown. Methods Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC. Results Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of β-catenin by decreasing its phosphorylation. The depletion of β-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells. Conclusions Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1.

Sign in / Sign up

Export Citation Format

Share Document