Ginsenoside Rg3 targets cancer stem cells and tumor angiogenesis to inhibit colorectal cancer progression in vivo

AbstractExploring novel anticancer drugs to optimize the efficacy may provide a benefit for the treatment of colorectal cancer (CRC). Disulfiram (DSF), as an antialcoholism drug, is metabolized into diethyldithiocarbamate-copper complex (CuET) in vivo, which has been reported to exert the anticancer effects on various tumors in preclinical studies. However, little is known about whether CuET plays an anti-cancer role in CRC. In this study, we found that CuET had a marked effect on suppressing CRC progression both in vitro and in vivo by reducing glucose metabolism. Mechanistically, using RNA-seq analysis, we identified ALDH1A3 as a target gene of CuET, which promoted cell viability and the capacity of clonal formation and inhibited apoptosis in CRC cells. MicroRNA (miR)-16-5p and 15b-5p were shown to synergistically regulate ALDH1A3, which was negatively correlated with both of them and inversely correlated with the survival of CRC patients. Notably, using co-immunoprecipitation followed with mass spectrometry assays, we identified PKM2 as a direct downstream effector of ALDH1A3 that stabilized PKM2 by reducing ubiquitination. Taken together, we disclose that CuET treatment plays an active role in inhibiting CRC progression via miR-16-5p and 15b-5p/ALDH1A3/PKM2 axis–mediated aerobic glycolysis pathway.

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Mesenchymal stem cells promote colorectal cancer progression through AMPK/mTOR-mediated NF-κB activation

Scientific Reports ◽

10.1038/srep21420 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 34

Author(s):

Xiao-Bing Wu ◽

Yang Liu ◽

Gui-Hua Wang ◽

Xiao Xu ◽

Yang Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Abstract B78: Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signaling

10.1158/1538-7445.chtme14-b78 ◽

2015 ◽

Author(s):

Olivier De Wever ◽

Astrid de Boeck

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Progression ◽

Neuregulin 1 ◽

Colorectal Cancer Progression

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LncRNA DQ786243 contributes to proliferation and metastasis of colorectal cancer both in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20160048 ◽

2016 ◽

Vol 36 (3) ◽

Cited By ~ 16

Author(s):

Longci Sun ◽

Hanbing Xue ◽

Chunhui Jiang ◽

Hong Zhou ◽

Lei Gu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Proliferation And Metastasis ◽

Non Coding Rnas ◽

Colorectal Cancer Progression

This article aims to find the key long non-coding RNAs (LncRNAs) associated with colorectal cancer (CRC) and to study its biological functions in colorectal cancer progression. Our study has shown that upregulated LncRNA DQ786243 can regulate cell proliferation, cell cycle progression, cell apoptosis, migration, and invasion in CRC cells. Xenograft experiments confirmed that the growth of xenograft tumors formed by CRC cells was suppressed after silencing LncRNA DQ786243 expression. In conclusion, our study suggests that LncRNA DQ786243 is an oncogene that promotes tumor progression and leads us to propose that LncRNAs may serve as key regulatory hubs in CRC progression.

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The Long Noncoding RNA HOTAIR Promotes Colorectal Cancer Progression by Sponging miR-197

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504017x15105708598531 ◽

2018 ◽

Vol 26 (3) ◽

pp. 473-481 ◽

Cited By ~ 18

Author(s):

Xinyang Lu ◽

Zhiqiang Liu ◽

Xiaofei Ning ◽

Lunhua Huang ◽

Biao Jiang

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Migration And Invasion ◽

Downstream Target ◽

Potential Applications ◽

Colorectal Cancer Progression

The long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been found to be overexpressed in many human malignancies and involved in tumor progression and metastasis. Although the downstream target through which HOTAIR modulates tumor metastasis is not well known, evidence suggests that microRNA-197 (miR-197) might be involved in this event. In the present study, the significance of HOTAIR and miR-197 in the progression of colorectal cancer was detected in vitro and in vivo. We found that HOTAIR expression was significantly increased in colorectal cancer cells and tissues. In contrast, the expression of miR-197 was obviously decreased. We further demonstrated that HOTAIR knockdown promoted apoptosis and inhibited cell proliferation, migration, and invasion in vitro and in vivo. Moreover, HOTAIR modulated the progression of colorectal cancer by competitively binding miR-197. Taken together, our study has identified a novel pathway through which HOTAIR exerts its oncogenic role and provided a molecular basis for potential applications of HOTAIR in the prognosis and treatment of colorectal cancer.

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Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling

Gut ◽

10.1136/gutjnl-2011-301393 ◽

2012 ◽

Vol 62 (4) ◽

pp. 550-560 ◽

Cited By ~ 97

Author(s):

Astrid De Boeck ◽

Patrick Pauwels ◽

Karen Hensen ◽

Jean-Luc Rummens ◽

Wendy Westbroek ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Progression ◽

Neuregulin 1 ◽

Colorectal Cancer Progression

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FTO-mediated cytoplasmic m6Am demethylation adjusts stem-like properties in colorectal cancer cell

Nature Communications ◽

10.1038/s41467-021-21758-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Sébastien Relier ◽

Julie Ripoll ◽

Hélène Guillorit ◽

Amandine Amalric ◽

Cyrinne Achour ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Messenger Rna ◽

Cancer Biology ◽

Biological Function ◽

Cancer Management ◽

Demethylase Activity

AbstractCancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N6,2’-O-dimethyladenosine (m6Am) demethylase activity. While m6Am is strategically located next to the m7G-mRNA cap, its biological function is not well understood and has not been addressed in cancer. Low FTO expression in patient-derived cell lines elevates m6Am level in mRNA which results in enhanced in vivo tumorigenicity and chemoresistance. Inhibition of the nuclear m6Am methyltransferase, PCIF1/CAPAM, fully reverses this phenotype, stressing the role of m6Am modification in stem-like properties acquisition. FTO-mediated regulation of m6Am marking constitutes a reversible pathway controlling CSC abilities. Altogether, our findings bring to light the first biological function of the m6Am modification and its potential adverse consequences for colorectal cancer management.

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