Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/β-catenin pathway

2020 ◽  
pp. 1-11
Author(s):  
Zhining Liu ◽  
Yimei Gu ◽  
Xiaohu Cheng ◽  
Heng Jiang ◽  
Yang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Progression ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues

Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, β-catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/β-catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/β-catenin signaling pathway.

scholarly journals MnTE-2-PyP Attenuates TGF-β-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Inhibiting the Smad2/3 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Yang ◽  
Pei Zhang ◽  
Ruicheng Yan ◽  
Qi Wang ◽  
Erhu Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Progression

Background. As a key step in enhancing cancer cell invasion and metastasis, epithelial-mesenchymal transition (EMT) plays an important role in colorectal cancer progression. EMT is triggered by a variety of signaling pathways, among which the transforming growth factor β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β in the presence or absence of MnTE-2-PyP. Cells were analyzed by several techniques including western blotting, real-time quantitative PCR, transwell assay, and wound healing assay. Results. MnTE-2-PyP reverses cell phenotypes induced by TGF-β in colon cancer cells. MnTE-2-PyP treatment significantly reduced the expression of mesenchymal markers but maintained epithelial marker expression. Mechanistically, MnTE-2-PyP suppressed the phosphorylated Smad2/3 protein levels induced by TGF-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-mediated cell migration and invasion and the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in colorectal cells. Conclusion. Taken together, we provide an in-depth mechanism by which MnTE-2-PyP inhibits colorectal cancer progression, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in colorectal cancer.

scholarly journals Serum DJ-1 Is a Biomarker of Colorectal Cancer and DJ-1 Activates Mitophagy to Promote Colorectal Cancer Progression

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4151
Author(s):  
William Tzu-Liang Chen ◽  
Han-Bin Yang ◽  
Tao-Wei Ke ◽  
Wen-Ling Liao ◽  
Shih-Ya Hung
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Adenocarcinoma ◽  
Reactive Oxygen Species Generation ◽  
Cancer Drug ◽  
Adenocarcinoma Cells ◽  
Colorectal Cancer Progression ◽  
Colorectal Cancer Patients

Colorectal cancer is the second most common cancer and the third cancer-associated death in Taiwan. Currently used serum markers for detecting colorectal cancer lack excellent diagnostic accuracy, which results in colorectal cancer being often recognized too late for successful therapy. Mitophagy is the selective autophagic degradation of damaged or excessive mitochondria. DJ-1 is an antioxidant protein that attenuates oxidative stress and maintains mitochondrial quality through activating mitophagy. Mitophagy activation contributes to anti-cancer drug resistance. However, the role of DJ-1-induced mitophagy in colorectal cancer progression remains unclear. In the present study, we collected matched tumor and adjacent normal tissues and serum from patients and cancer cells to demonstrate the clinical value and physiological function of DJ-1 in colorectal cancer. We found that DJ-1 increased in tumor tissues and serum; it was positively correlated with TNM (tumor-node-metastasis) stages of colorectal cancer patients. Through stable knockdown DJ-1 expression in metastatic colorectal adenocarcinoma cells SW620, DJ-1 knockdown inhibited cancer cell survival, migration, and colony formation. In SW620 cells, DJ-1 knockdown induced an incomplete autophagic response that did not affect ATP production; DJ-1 knockdown enhanced intracellular reactive oxygen species generation and damaged mitochondrial accumulation and mitophagy inhibition. It suggests that DJ-1 knockdown inhibits mitophagy that causes metastatic colorectal adenocarcinoma cells to be unable to remove damaged mitochondria and further enhance cancer cell apoptosis. Our data indicate that DJ-1 might be clinically valuable as serum and tissue biomarkers for predicting the TNM stage in colorectal cancer patients. Since DJ-1-induced mitophagy promotes tumor progression, DJ-1 inhibition is a potential therapeutic strategy for colorectal cancer treatment.

Hypoxic colorectal cancer-secreted exosomes deliver miR-210-3p to normoxic tumor cells to elicit a protumoral effect

2021 ◽  
pp. 153537022110115
Author(s):  
Liuqing Ge ◽  
Feng Zhou ◽  
Jiayan Nie ◽  
Xiaobing Wang ◽  
Qiu Zhao
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Preclinical Study ◽  
Mechanistic Investigation ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Progression

Hypoxia, the most common feature in the tumor microenvironment, is closely related to tumor malignant progression and poor patient’s prognosis. Exosomes, initially recognized as cellular “garbage dumpsters”, are now known to be important mediums for mediating cellular communication in tumor microenvironment. However, the mechanisms of hypoxic tumor cell-derived exosomes facilitate colorectal cancer progression still need further exploration. In the present study, we found that exosomes from hypoxic colorectal cancer cells (H-Exos) promoted G1-S cycle transition and proliferation while preventing the apoptosis of colorectal cancer cells by transmitting miR-210-3p to normoxic tumor cells. Mechanistic investigation indicated that miR-210-3p from H-Exos elicited its protumoral effect via suppressing CELF2 expression. A preclinical study further confirmed that H-Exos could promote tumorigenesis in vivo. Clinically, the expression of miR-210-3p in circulating plasma exosomes was markedly upregulated in colorectal cancer patients, which were closely associated with multiple unfavorable clinicopathological features. Taken together, these results suggest that hypoxia may stimulate colorectal cancer cells to secrete miR-210-3p-enriched exosomes in tumor microenvironment, which elicit protumoral effects by inhibiting CELF2 expression. These findings provide new insights on the mechanism of colorectal cancer progression and potential therapeutic targets for colorectal cancer.

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

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769430 ◽  
Author(s):  
Meifeng Zhang ◽  
Wei Wu ◽  
Ming Gao ◽  
Jie Zhang ◽  
Xinde Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Human Colorectal Cancer ◽  
Arginine Methyltransferase ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Methyltransferase 1

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.

scholarly journals Potentiating Effect of Oxymatrine and 5-fluorouracil on Cell Survival and Inhibition of Cancer Metastasis in SW-620 Colorectal Cancer Cells

2017 ◽  
Vol 15 (2) ◽  
pp. 117-130
Author(s):  
Suwisit MANMUAN ◽  
Punyo YOYKAEW ◽  
Piyachat THUETONG ◽  
Patchraporn ASIPONG ◽  
Nattanicha RIANTONG
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cell Viability ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cell Invasion ◽  
Response Rate ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Patients

Colorectal cancer (CRC) is the most common cancer in the world, beginning in the cell lining of the colon and rectum. 5-fluorouracil (5-FU) is a first-line therapy for colorectal cancer patients. However, the response rate of 5-FU in advanced colorectal cancer patients is only 10 - 15 %, and can fail due to drug resistance. Therefore, the development of a new anticancer compound for improving the response rate or for reversing resistance to 5-FU is urgently needed. Oxymatrine is a major component of Sophora flavescens. Recently, many pharmacological effects have been exhibited. The objectives of the present study were to investigate the anticancer activity of oxymatrine, as well as to potentiate the effect of oxymatrine with 5-FU on cell viability, colony-forming, cell migration, cell invasion, and determined MMP-9 protein expression in SW-620 colorectal cancer cells. The results demonstrated that oxymatrine significantly inhibited the cell viability of SW-620 cells after 24, 48, and 72 h treatments. Oxymatrine and 5-FU interaction was synergistically greater in inhibiting the cell survival of SW-620 cells than 5-FU was alone. Oxymatrine also decreased colony formation, cell migration, and cell invasion through reducing the level of MMP-9 protein in SW-620 cells. These first findings elucidated an efficacious anticancer agent, which is derived from natural sources, which could be used to overcome 5-FU resistance in colorectal cancer, and may be beneficial for patients with colorectal cancer who are treated with 5-FU.

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 Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF

2021 ◽  
Author(s):  
Zahra Nouri Ghonbalani ◽  
Shiva Shahmohamadnejad ◽  
Parvin Pasalar ◽  
Ehsan Khalili
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Promoter Region ◽  
Hct116 Cell ◽  
Methylation Status ◽  
Expression Level ◽  
Cancer Tissue ◽  
Vegf Expression ◽  
Cancer Tissues

Abstract PurposeColorectal cancer (CRC) is the second leading cause of death from cancer in adults. Recent advances have shown that cancer cells can have some epigenetic changes involved in all stages of cancer. It has also been shown that miR-424 acts as gene expression regulators in many biological processes, including angiogenesis with mediators such as VEGF. In the current study, to identify the potential role of miR-424 in colorectal cancer progression, methylation status of miR-424 promoter region and its expression level have been evaluated. Besides, the correlation between VEGF level and miR-424 expression level has been assessed.MethodsMethylation status miR-424 promoter was assessed using methylation-specific polymerase chain reaction (MSP). The expression level of miR-424 in human colorectal cancer tissue was analyzed by quantitative PCR. HCT116 cell line was selected to evaluate the correlation between the miR-424 expression level and the promoter's methylation status. VEGF expression, one out of mir-424 targets involved in angiogenesis and cancer progression, was measured by western blot analysis in the pairs of cancer tissues and their adjacent tissues.ResultsOur results have revealed that the promoter region of miR-424 is methylated in cancer cells compared to normal cells, leading to down-regulation of miR-424 in the colorectal cancer tissues compared to the normal tissues. Also, we found that the expression protein's level of VEGF in the tumor cells increased compared with normal tissues.ConclusionThe present study suggests that hypermethylation downregulates miR-424. VEGF expression is upregulated with decreased miR-424 in colorectal cancer, which results in cancer progression.

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