Overexpression of DDIT4 and TPTEP1 are associated with metastasis and advanced stages in colorectal cancer patients: a study utilizing bioinformatics prediction and experimental validation

Abstract Background Various diagnostic and prognostic tools exist in colorectal cancer (CRC) due to multiple genetic and epigenetic alterations causing the disease. Today, the expression of RNAs is being used as prognostic markers for cancer. Methods In the current study, various dysregulated RNAs in CRC were identified via bioinformatics prediction. Expression of several of these RNAs were measured by RT-qPCR in 48 tissues from CRC patients as well as in colorectal cancer stem cell-enriched spheroids derived from the HT-29 cell line. The relationships between the expression levels of these RNAs and clinicopathological features were analyzed. Results Our bioinformatics analysis determined 11 key mRNAs, 9 hub miRNAs, and 18 lncRNAs which among them 2 coding RNA genes including DDIT4 and SULF1 as well as 3 non-coding RNA genes including TPTEP1, miR-181d-5p, and miR-148b-3p were selected for the further investigations. Expression of DDIT4, TPTEP1, and miR-181d-5p showed significantly increased levels while SULF1 and miR-148b-3p showed decreased levels in CRC tissues compared to the adjacent normal tissues. Positive relationships between DDIT4, SULF1, and TPTEP1 expression and metastasis and advanced stages of CRC were observed. Additionally, our results showed significant correlations between expression of TPTEP1 with DDIT4 and SULF1. Conclusions Our findings demonstrated increased expression levels of DDIT4 and TPTEP1 in CRC were associated with more aggressive tumor behavior and more advanced stages of the disease. The positive correlations between TPTEP1 as non-coding RNA and both DDIT4 and SULF1 suggest a regulatory effect of TPTEP1 on these genes.

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Expression of Migration-Related Genes in Human Colorectal Cancer and Activity of a Disintegrin and Metalloproteinase 17

BioMed Research International ◽

10.1155/2016/8208904 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Katarzyna Walkiewicz ◽

Paweł Kozieł ◽

Martyna Bednarczyk ◽

Adam Błażelonis ◽

Urszula Mazurek ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Markers ◽

Microarray Data Analysis ◽

Human Colorectal Cancer ◽

Normal Tissues ◽

Significance Analysis ◽

Expression Of Genes ◽

Advanced Stages ◽

A Disintegrin And Metalloproteinase ◽

Colorectal Cancer Patients

Introduction.The ability to form metastases which depends on the mechanisms of cell migration is an important element of the progression of cancer. In the present study we analyzed the genes involved in the regulation of migration in colon cancer cells.Materials and Methods.A total of 20 pairs of surgically removed tumoral and healthy (marginal) tissues samples from colorectal cancer patients at clinical stages I-II and III-IV were analyzed. The isolation of RNA from CRC and normal tissues and its subsequent molecular analysis were performed according to manufacturer’s instructions. Microarray data analysis was performed using the GeneSpring 11.5 platform and Significance Analysis of Microarrays (SAM). In SAM analysis to identify significantly differentially expressed genes score andq-value parameters were used.Results.The largest increase in expression of genes was shown by MMP9, ADAM17, EphA2, and TIMP.Conclusions.Presented genes, especially ADAM17, MMP9, EphA2, TIMP1, ICAM 11, and CD4, may be used as prognostic markers of advanced stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor.

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Long Non-Coding RNA CBR3-AS1 Promotes Stem-Like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p

10.21203/rs.3.rs-58142/v1 ◽

2020 ◽

Author(s):

Liangbao Xie ◽

Guangfei Cui ◽

Tao Li

Keyword(s):

Colorectal Cancer ◽

Direct Interaction ◽

Luciferase Reporter ◽

Expression Levels ◽

Mammosphere Formation ◽

Normal Tissues ◽

Non Coding Rna ◽

Rna Immunoprecipitation ◽

Long Non Coding Rna

Abstract Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.

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Clock Gene Expression Levels and Relationship With Clinical and Pathological Features in Colorectal Cancer Patients

Chronobiology International ◽

10.3109/07420528.2011.615182 ◽

2011 ◽

Vol 28 (10) ◽

pp. 841-851 ◽

Cited By ~ 76

Author(s):

G. Mazzoccoli ◽

A. Panza ◽

M. R. Valvano ◽

O. Palumbo ◽

M. Carella ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cancer Patients ◽

Clock Gene ◽

Pathological Features ◽

Expression Levels ◽

Clock Gene Expression ◽

Colorectal Cancer Patients ◽

Clinical And Pathological Features ◽

Gene Expression Levels

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The Effect of miR-145-5p, DANCR and NRAS Expression Levels on the Survival Rate of Colorectal Cancer Patients

Asian Pacific Journal of Cancer Prevention ◽

10.31557/apjcp.2021.22.12.4043 ◽

2021 ◽

Vol 22 (12) ◽

pp. 4043-4049

Author(s):

Fatemeh Bahreini ◽

Masoud Saidijam ◽

Saeid Afshar ◽

Zahra Mousivand ◽

Rezvan Najafi

Keyword(s):

Colorectal Cancer ◽

Survival Rate ◽

Cancer Patients ◽

Expression Levels ◽

Colorectal Cancer Patients

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The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽

10.1159/000519913 ◽

2022 ◽

pp. 1-10

Author(s):

Cheng Yang ◽

Na Xie ◽

Zhifei Luo ◽

Xiling Ruan ◽

Yixin Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Protein Expression ◽

Poor Prognosis ◽

Cancer Metastasis ◽

Mrna Level ◽

Normal Mucosa ◽

Tnm Stage ◽

Expression Levels ◽

Normal Tissues

Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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Long non-coding RNA AGER-1 inhibits colorectal cancer progression through sponging miR-182

The International Journal of Biological Markers ◽

10.1177/1724600819897079 ◽

2020 ◽

Vol 35 (1) ◽

pp. 10-18 ◽

Cited By ~ 1

Author(s):

Mingzhu Lin ◽

Yinyan Li ◽

Jianfeng Xian ◽

Jinbin Chen ◽

Yingyi Feng ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Ectopic Expression ◽

Tumor Development ◽

Vital Role ◽

Normal Tissues ◽

Non Coding Rna ◽

Colorectal Cancer Progression ◽

And Migration ◽

Long Non Coding Rna

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = −0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.

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Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21197120 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7120

Author(s):

Anna Panza ◽

Stefano Castellana ◽

Giuseppe Biscaglia ◽

Ada Piepoli ◽

Luca Parca ◽

...

Keyword(s):

Colorectal Cancer ◽

Chromosomal Translocation ◽

Normal Tissues ◽

Novel Transcript ◽

Non Coding Rna ◽

Genomic Landscape ◽

Potential Biomarker ◽

Fusion Analysis ◽

Long Non Coding Rna ◽

Increased Activity

Fusion genes and epigenetic regulators (i.e., miRNAs and long non-coding RNAs) constitute essential pieces of the puzzle of the tumor genomic landscape, in particular in mechanisms behind the adenoma-to-carcinoma progression of colorectal cancer (CRC). In this work, we aimed to identify molecular signatures of the different steps of sporadic CRC development in eleven patients, of which synchronous samples of adenomas, tumors, and normal tissues were analyzed by RNA-Seq. At a functional level, tumors and adenomas were all characterized by increased activity of the cell cycle, cell development, cell growth, and biological proliferation functions. In contrast, organic survival and apoptosis-related functions were inhibited both in tumors and adenomas at different levels. At a molecular level, we found that three individuals shared a tumor-specific fusion named MRPS31-SUGT1, generated through an intra-chromosomal translocation on chromosome 13, whose sequence resulted in being 100% identical to the long non-coding RNA (lncRNA) MRPS31P5. Our analyses suggest that MRPS31P5 could take part to a competitive endogenous (ce)RNA network by acting as a miRNA sponge or/and as an interactor of other mRNAs, and thus it may be an important gene expression regulatory factor and could be used as a potential biomarker for the detection of early CRC events.

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