scholarly journals Identification of Motile Sperm Domain Containing 1 (MOSPD1) As a Novel Target of the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

2021 ◽  
Author(s):  
Chiaki Horie ◽  
Chi Zhu ◽  
Kiyoshi Yamaguchi ◽  
Saya Nakagawa ◽  
Kiyoko Takane ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Regulatory Region ◽  
Motile Sperm ◽  
Enhancer Activity ◽  
Binding Motifs ◽  
Direct Target ◽  
Flanking Region ◽  
Novel Target ◽  
Cancer Tissues

Abstract Aberrant activation of the Wnt/β-catenin signaling pathway plays a crucial role in the development and progression of colorectal cancer. Previously, we identified a set of candidate genes that were regulated by this signaling pathway, and we focused on MOSPD1, motile sperm domain containing 1, in this study. Immunohistochemical staining revealed that the expression of MOSPD1 was elevated in tumorous cells of colorectal cancer tissues compared with non-tumorous cells. Using ChIP-seq data and JASPAR database, we searched for the regulatory region(s) in the MOSPD1 gene as a target of the Wnt/β-catenin signaling, and identified a region containing three putative TCF-binding motifs in the 3’-flanking region. Additional analyses using reporter assay and ChIP-qPCR suggested that this region harbors an enhancer activity through an interaction with TCF7L2 and β-catenin. These data have clarified that MOSPD1 is a novel direct target of the Wnt/β-catenin signaling. In addition, the identification of its enhancer region may be helpful for the future studies of precise regulatory mechanisms of MOSPD1.

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 MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769502 ◽  
Author(s):  
Taiwei Jiao ◽  
Yue Li ◽  
Tong Gao ◽  
Yining Zhang ◽  
Mingliang Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Wnt Signaling Pathway ◽  
Lovo Cell ◽  
Induced Apoptosis ◽  
Cancer Tissues

MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.

Single Investigation of the Role of APC2 in Colorectal Cancer

2020 ◽  
Author(s):  
Yingwei Jiao ◽  
Qiang Liu ◽  
Hongbo Zhao ◽  
Xianzhen Hu ◽  
Jinlong Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Invasion ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Mrna Levels ◽  
Colorectal Cancer Cell Lines ◽  
Cancer Tissues

Abstract BackgroundAPC2 is as a homolog of adenomatous polyposis coli (APC) that has comparable functions in cancer, and is located on chromosome 19p13.3. It is an important signaling pathway protein in many cancers and diseases. For example, in ovarian cancer, APC2 serves as an important tumor suppressor through the induction of the WNT signaling pathway, inhibiting tumor invasion and growth. In colorectal cancer, APC2 was shown to be an important protein for inhibiting tumor invasion and metastasis. In the present study, APC2 was shown to be an important regulatory pathway protein that cooperates with microRNA bidirectional regulation to induce phenotypic changes in colorectal cancer.MethodsThrough measurements in colorectal cancer tissue samples (RT-PCR and immunohistochemistry), we found that the APC2 gene may play a role in the occurrence and development of colorectal cancer patients. We selected colorectal cancer cell lines as the research carrier of the APC2 gene. We changed the expression of APC2 gene in colorectal cancer cell lines by silencing the APC2 gene and up-regulating the APC2 gene, and then used cell cycle, MTT and western blot methods to measure its possible effects on colorectal cancer mechanisms.ResultWe found that the expression of APC2 in normal mucosal tissues in colorectal cancer tissues is was than that of matched colorectal cancer tissues, both at the protein and mRNA levels. We then tested colorectal cancer cell lines for gene silencing and up-regulation. We found that silencing the expression of the APC2 gene effectively advanced the cycle in colorectal cancer cells. In subsequent protein testing, we found that the proteins of the relevant cycle checkpoints changed accordingly. We found the opposite in cell lines after up-regulating the expression of the APC2 gene. By contrast, the SW480 cell line with k-ras mutation in the key pathway did not produce relevant changes by up-regulating the expression of the APC2 gene.ConclusionLow expression levels of the APC2 gene in colorectal cancer inhibit the progression of colorectal cancer cell lines through the RAS signaling pathway and hinders the occurrence and development of colorectal cancer.

scholarly journals CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer via Inhibiting JAK-STAT Signaling Pathway

2021 ◽  
Vol 10 ◽  
Author(s):  
Biyin Chen ◽  
Li Song ◽  
Xiuzhen Nie ◽  
Fangfeng Lin ◽  
Zongyang Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Potential Therapeutic Target ◽  
Transwell Invasion Assay ◽  
Stat Signaling ◽  
Direct Target ◽  
Dual Luciferase Reporter Assay

PurposeThis study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).MethodsBioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.ResultsCXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors via activation of JAK-STAT signaling pathway.ConclusionCXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.

scholarly journals Risk SNP-induced lncRNA-SLCC1 drives colorectal cancer through activating glycolysis signaling

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tingting Yan ◽  
Chaoqin Shen ◽  
Penglei Jiang ◽  
Chenyang Yu ◽  
Fangfang Guo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Patient Survival ◽  
Colorectal Carcinogenesis ◽  
Binding Motif ◽  
Poor Survival ◽  
Enhancer Activity ◽  
Glycolysis Pathway ◽  
Non Coding Rnas ◽  
Cancer Tissues

AbstractLong non-coding RNAs (lncRNAs) play key roles in colorectal carcinogenesis. Here, we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis. First, we identified rs6695584 as the causative SNP in 1q41 locus. The A>G mutation of rs6695584 created a protein-binding motif of BATF, altered the enhancer activity, and subsequently activated lncSLCC1 expression. Further validation in two independent CRC cohorts confirmed the upregulation of lncSLCC1 in CRC tissues, and revealed that increased lncSLCC1 expression was associated with poor survival in CRC patients. Mechanistically, lncRNA-SLCC1 interacted with AHR and transcriptionally activated HK2 expression, the crucial enzyme in glucose metabolism, thereby driving the glycolysis pathway and accelerating CRC tumor growth. The functional assays revealed that lncSLCC1 induced glycolysis activation and tumor growth in CRC mediated by HK2. In addition, HK2 was upregulated in colorectal cancer tissues and positively correlated with lncSLCC1 expression and patient survival. Taken together, our findings reveal a risk SNP-mediated oncogene lncRNA-SLCC1 promotes CRC through activating the glycolysis pathway.

Orai1, a Direct Target of microRNA-519, Promotes Progression of Colorectal Cancer via Akt/GSK3β Signaling Pathway

2016 ◽  
Vol 61 (6) ◽  
pp. 1553-1560 ◽  
Author(s):  
Wei Deng ◽  
Jin Wang ◽  
Jun Zhang ◽  
Jun Cai ◽  
Zhigang Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Direct Target

Mutation Detection of K-ras Gene in Paraffin-embedded Colorectal Cancer Tissues by Using Chip-based TGCE*

2010 ◽  
Vol 37 (7) ◽  
pp. 794-800 ◽  
Author(s):  
Hui-Dan ZHANG ◽  
Xiao-Nan WANG ◽  
Zhe ZHOU ◽  
Qian MA ◽  
Jin FANG
Keyword(s):  
Colorectal Cancer ◽  
Mutation Detection ◽  
Cancer Tissues ◽  
I Gene

scholarly journals Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Anna E. M. Bastiaansen ◽  
A. Mieke Timmermans ◽  
Marcel Smid ◽  
Carolien H. M. van Deurzen ◽  
Esther S. P. Hulsenboom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Glutamate Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate ◽  
Metabotropic Glutamate Receptor 1 ◽  
Novel Target ◽  
Cancer Tissues

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

scholarly journals Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382199007
Author(s):  
Wenlin Liu ◽  
Jiandong Zhan ◽  
Rong Zhong ◽  
Rui Li ◽  
Xiaoli Sheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Laryngeal Cancer ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

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