Dataset Information

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis.

ABSTRACT: Background:Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Successful treatment of CRC relies on accurate early diagnosis, which is currently a challenge due to its complexity and personalized pathologies. Thus, novel molecular biomarkers are needed for early CRC detection. Methods:Gene and microRNA microarray profiling of CRC tissues and miRNA-seq data were analyzed. Candidate microRNA biomarkers were predicted using both CRC-specific network and miRNA-BD tool. Validation analyses were carried out to interrogate the identified candidate CRC biomarkers. Results:We identified miR-451a as a potential early CRC biomarker circulating in patient's serum. The dysregulation of miR-451a was revealed both in primary tumors and in patients' sera. Downstream analysis validated the tumor suppressor role of miR-451a and high sensitivity of miR-451a in CRC patients, further confirming its potential role as CRC circulation biomarker. Conclusion:The miR-451a is a potential circulating biomarker for early CRC diagnosis.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7474364 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis.

Zhang Zhen Z Zhang Dai D Cui Yaping Y Qiu Yongsheng Y Miao Changhong C Lu Xihua X

BioMed research international 20200827

<h4>Background</h4>Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Successful treatment of CRC relies on accurate early diagnosis, which is currently a challenge due to its complexity and personalized pathologies. Thus, novel molecular biomarkers are needed for early CRC detection.<h4>Methods</h4>Gene and microRNA microarray profiling of CRC tissues and miRNA-seq data were analyzed. Candidate microRNA biomarkers were predicted using both CRC-specific network and m ...[more]

PMID: 32908896

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Project description:BackgroundColorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation.MethodsIn this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student's T-tests for simple comparisons and two-factor ANOVA for evaluating significance.ResultsThe most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival.ConclusionsTaken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways.

Project description:BackgroundColorectal cancer (CRC) is the third most lethal and malignant type of cancer in the world. Abnormal expression of human microRNA-200a (hsa-miRNA-200a or miR-200a) has previously been characterized as a clinically noticeable biomarker in several cancers, but its role in CRC is still unclear.MethodsThree CRC miRNA expression datasets were integratively analyzed by Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Nine candidate miRNAs were identified and validated for diagnostic and prognostic capability with the prediction model. The potential roles of the tumor suppressor miR-200a-3p in invasion, migration, and epithelial-mesenchymal transition of CRC cells were elaborated by in vitro studies.ResultsNine miRNAs (miR-492, miR-200a, miR-338, miR-29c, miR-101, miR-148a, miR-92a, miR-424, and miR-210) were identified as potentially useful diagnostic biomarkers in the clinic. The overall accuracy rate of the nine miRNAs in the diagnostic model was 0.94, 0.89, and 0.978 in the testing, validation, and independent validation dataset, respectively. CRC patients in the GSE29622 cohort were separated by the prognostic model into the low-risk score group and the high-risk score group. The area under the receiver operating characteristic curve (AUC) was 0.872 and 0.783 for predicting the 1- to 10-year survival of CRC patients. The performance of the prognostic model was validated by an independent TCGA-Colon Adenocarcinoma (COAD) dataset with AUC values between 0.911 and 0.796 in predicting 1- to 10-year survival. Nomograms comprising risk scores, tumor stage, and TNM staging were generated for predicting 1-, 3-, and 5-year overall survival (OS) in the GSE29622 and TCGA-COAD datasets. Colony formation, invasion, and migration in DLD1 and SW480 cells were suppressed by overexpression of miR-200a-3p. Inhibition of miR-200a-3p function contributed to abnormal colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT). miR-200a-3p binding sites were located within the 3'-untranslated region (3'-UTR) of the Forkhead box protein A1 (FOXA1) mRNA.ConclusionWe developed and validated a diagnostic and prognostic prediction model for CRC. miR-200a-3p was determined to be a potential diagnostic and prognostic biomarker for CRC.

Dataset Information

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis.

Publications

Identification of microRNA-451a as a Novel Circulating Biomarker for Colorectal Cancer Diagnosis.

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