Dataset Information

FOXM1 and FOXQ1 Are Promising Prognostic Biomarkers and Novel Targets of Tumor-Suppressive miR-342 in Human Colorectal Cancer.

ABSTRACT: Colorectal cancer ranks as the third most frequent cancer type, and its incidence continues to rise gradually worldwide, highlighting the need to identify previously unrecognized molecular events that propel development of this malignancy. Recent evidence suggests that dysregulated expression of FOX family of transcription factors may be critical in various genetic disorders as well as cancer; however, the functional and clinical significance of this pathway in colorectal cancer remains unclear.Herein, we performed a systematic and comprehensive discovery step by evaluating the expression of FOX family members, and identified that FOXM1 and FOXQ1 are frequently overexpressed in colorectal cancer. We subsequently confirmed these findings in two large testing cohorts (n = 550) and an independent clinical validation cohort (n = 134), in which high expression of FOXM1 and FOXQ1 emerged as an independent prognostic factor in colorectal cancer patients. We corroborated these findings by performing functional assays in which knockdown of FOXM1 and FOXQ1 resulted in inhibited cell proliferation and suppressed migration and invasion in colorectal cancer cells. Furthermore, using bioinformatic approaches, we identified miR-342 as a novel regulator of both FOXM1 and FOXQ1. Overexpression or inhibition of miR-342 modulated the expression of both genes and contributed to phenotypic alterations in colorectal cancer cells, which was subsequently validated in a xenograft animal model.Collectively, we have firstly identified FOXM1 and FOXQ1 as promising prognostic biomarkers in colorectal cancer patients, and provided novel evidence that therapeutic targeting of these genes or miR-342 may be a potential treatment approach in colorectal cancer patients. Clin Cancer Res; 22(19); 4947-57. ©2016 AACR.

SUBMITTER: Weng W

PROVIDER: S-EPMC5435114 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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FOXM1 and FOXQ1 Are Promising Prognostic Biomarkers and Novel Targets of Tumor-Suppressive miR-342 in Human Colorectal Cancer.

Weng Wenhao W Okugawa Yoshinaga Y Toden Shusuke S Toiyama Yuji Y Kusunoki Masato M Goel Ajay A

Clinical cancer research : an official journal of the American Association for Cancer Research 20160509 19

<h4>Purpose</h4>Colorectal cancer ranks as the third most frequent cancer type, and its incidence continues to rise gradually worldwide, highlighting the need to identify previously unrecognized molecular events that propel development of this malignancy. Recent evidence suggests that dysregulated expression of FOX family of transcription factors may be critical in various genetic disorders as well as cancer; however, the functional and clinical significance of this pathway in colorectal cancer ...[more]

PMID: 27162244

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Project description:BackgroundEarly detection of colorectal neoplasms, including colorectal cancers (CRCs) and advanced colorectal adenomas (AAs), is crucial to improve patient survival. Circulating microRNAs (miRNAs) in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers, but their potential for screening colorectal neoplasms remains ambiguous.AimTo identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.MethodsThe study was divided into three phases: (1) Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods; (2) an independent set of serum samples from 60 CRC patients, 60 AA patients and 30 healthy controls (HCs) was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs, and their diagnostic power was detected by receiver operating characteristic (ROC) analysis; and (3) the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.ResultsBased on bioinformatics analysis, miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study. Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs. The diagnostic power of miR-672-5p yielded an area under the curve (AUC) value of 0.90, and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs. A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA. Additionally, the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines, suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived. Furthermore, in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.ConclusionSerum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.

Dataset Information

FOXM1 and FOXQ1 Are Promising Prognostic Biomarkers and Novel Targets of Tumor-Suppressive miR-342 in Human Colorectal Cancer.

Publications

FOXM1 and FOXQ1 Are Promising Prognostic Biomarkers and Novel Targets of Tumor-Suppressive miR-342 in Human Colorectal Cancer.

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