Coactivator-associated arginine methyltransferase 1 promotes cell growth and is targeted by microRNA-195-5p in human colorectal cancer

The pathogenesis of colorectal cancer remains poorly understood. Here, we show that coactivator-associated arginine methyltransferase 1 is frequently upregulated in colorectal cancer tissues and promotes cell growth in vitro and in vivo. Using bioinformatics-based prediction and luciferase reporter system, we found that coactivator-associated arginine methyltransferase 1 is post-transcriptionally targeted by microRNA-195-5p in colorectal cancer. Ectopic expression of microRNA-195-5p led to the suppression of the coactivator-associated arginine methyltransferase 1 3′-untranslated regions activity and downregulation of the endogenous coactivator-associated arginine methyltransferase 1 protein in colorectal cancer cells. Expression analysis verified that microRNA-195-5p was markedly downregulated in human colorectal cancer tissues, which was negatively correlated with the elevated levels of coactivator-associated arginine methyltransferase 1 protein. Enhanced levels of microRNA-195-5p in colorectal cancer cells resulted in a sharp reduction of cell proliferative and colony-formative capacities in vitro. Remarkably, restoration of coactivator-associated arginine methyltransferase 1 in microRNA-195-5p-transfected colorectal cancer cells partially abrogated the inhibition of cell proliferation and colony formation mediated through microRNA-195-5p. These data confirm that microRNA-195-5p might function as an anti-tumor microRNA in colorectal cancer exerting critical control over coactivator-associated arginine methyltransferase 1 expression. The newly identified microRNA-195-5p/coactivator-associated arginine methyltransferase 1 axis may act as a novel promising therapeutic target for colorectal cancer treatment.

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Dehydrodiisoeugenol inhibits colorectal cancer growth by endoplasmic reticulum stress-induced autophagic pathways

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01915-9 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Changhong Li ◽

Kui Zhang ◽

Guangzhao Pan ◽

Haoyan Ji ◽

Chongyang Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Endoplasmic Reticulum ◽

Cell Growth ◽

Er Stress ◽

Cancer Cells ◽

Tumor Xenograft ◽

Anticancer Activities ◽

Colorectal Cancer Cells

Abstract Background Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated. Methods In this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo. Results Our findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models. Conclusions Collectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.

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

BioMed Research International ◽

10.1155/2013/867537 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 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.

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Action of a library of O-glycosylation inhibitors on the growth of human colorectal cancer cells in culture

Biochemical Society Transactions ◽

10.1042/bst0330721 ◽

2005 ◽

Vol 33 (4) ◽

pp. 721-723 ◽

Cited By ~ 11

Author(s):

G. Patsos ◽

V. Hebbe-Viton ◽

R. San Martin ◽

C. Paraskeva ◽

T. Gallagher ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Cell Lines ◽

Growth Patterns ◽

Limited Information ◽

Human Colorectal Cancer ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cells ◽

Colorectal Cancer Cell Lines

O-glycosylation is thought to play a significant role in the regulation of cell growth. However, only limited information is available, and few specific and selective inhibitors have been found. We have synthesized a library of O-glycosylation inhibitors based on benzyl-O-N-acetyl-D-galactosamine. These inhibitors were tested with an established series of human colorectal cancer cell lines, which model the adenoma-carcinoma sequence. Cancer cells were incubated with the inhibitors, and examined for cell growth patterns, and cellular and subcellular glycosylation using a range of lectins with confocal microscopy. The specificity of O-glycan inhibition was confirmed for the library, relative to other forms of glycosylation. All inhibitors tested resulted in smaller cell yields. However, a differential effect on O-glycosylation was detected using the lectins showing variation of localization at a subcellular level in the various cell lines. Further differential action of the inhibitor library was observed for apoptosis and on the cell cycle with the cell lines tested. This work demonstrates that O-glycosylation is closely involved in the regulation of cell growth in colorectal cancer cells and that the generation of a library of low-molecular-mass inhibitors offers a valuable means of examining this regulation at the molecular level.

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Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells

Molecular Carcinogenesis ◽

10.1002/mc.20374 ◽

2008 ◽

Vol 47 (3) ◽

pp. 197-208 ◽

Cited By ~ 118

Author(s):

Seong-Ho Lee ◽

Maria Cekanova ◽

Seung Joon Baek

Keyword(s):

Colorectal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Growth Arrest ◽

Human Colorectal Cancer ◽

Cell Growth Arrest ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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CircABCC4 Regulates the Proliferation, Migration, and Invasion of Colorectal Cancer SW620 Cells by Targeting Micro RNA-216a-3p

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2605 ◽

2021 ◽

Vol 11 (3) ◽

pp. 548-552

Author(s):

Yiqian Li ◽

Haofeng Yuan ◽

Yibin Chen ◽

Baoqi Xu ◽

Yanhong Zhang

Keyword(s):

Colorectal Cancer ◽

Micro Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Human Colorectal Cancer ◽

Cell Behaviors ◽

Colorectal Cancer Cells ◽

Sw620 Cells ◽

Cancer Tissues ◽

Dual Luciferase Reporter Assay

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

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