MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer

Abstract

Approximately 30–50% of colorectal cancer (CRC) patients who undergo curative resection subsequently experience tumor recurrence or metastasis. Although microRNAs (miRNAs) are a class of small noncoding RNAs frequently deregulated in various human malignancies, it remains unknown if these can help predict recurrence and metastasis in CRC patients. MiRNAs were initially screened using miRNA-microarray and miRNA-seq datasets with or without recurrence. Candidate miRNAs were then tested in two independent cohorts of 111 stage II/III and 139 stage I-III CRC patients, as well as serum samples and matched primary and metastatic liver tissues. An animal model of peritoneal dissemination was used to assess the oncogenic role of the target miRNA. Four candidate miRNAs were identified during the initial screening, and we subsequently validated upregulation of miR-139-5p in two independent clinical cohorts, wherein it associated with poor recurrence-free survival. Moreover, miR-139-5p were also upregulated in the serum of recurrence-positive CRC patients and yielded significantly shorter recurrence-free survival. Intriguingly, miR-139-5p was upregulated in metastatic liver tissues and negatively correlated with genes associated with epithelial-mesenchymal transition. Lastly, we showed that miR-139-5p overexpression enhanced peritoneal dissemination in a mouse model. In conclusion, we identified miR-139-5p as a novel biomarker for tumor recurrence and metastasis in CRC.

MiR‐483‐5p and miR‐139‐5p promote aggressiveness by targeting N‐myc downstream‐regulated gene family members in adrenocortical cancer

“…Although we do not have explanation for this discrepancy, one should mention that in Ozata's study, the concentrations of miRNA inhibitors used are 20 times higher than those we have tested in the present work . MiR‐139‐5p, which resides within intron 2 of PDE2A gene, has been reported to be downregulated and to display anti‐oncogenic and anti‐metastatic activities in human cancers . We found that miR‐139‐5p is upregulated in ACC patient samples as well as in NCI H295R cells in which it acts as pro‐invasive miRNA.…”

“…15 MiR-139-5p, which resides within intron 2 of PDE2A gene, has been reported to be downregulated and to display anti-oncogenic and antimetastatic activities in human cancers. 40 We found that miR-139-5p is upregulated in ACC patient samples as well as in NCI H295R cells in which it acts as pro-invasive miRNA. Our result showing for the first time that miR-139-5p is a powerful prognostic factor for survival of ACC patients supports its role in ACC aggressiveness.…”

Comparison of miR‐16 and cel‐miR‐39 as reference controls for serum miRNA normalization in colorectal cancer

“…Miyoshi et al, 6 who reported miR-139-5p upregulation in the serum samples of recurrence-positive CRC patients, added 25 fmol of cel-miR-39 to each sample for data normalization. Cel-miR-39, which is derived from Caenorhabditis elegans, is a synthetic microRNA that is used for microRNA normalization in the recent studies, and in this section we summarize some of the research that normalized values using cel-miR-39.…”

“…Cel-miR-39, which is derived from Caenorhabditis elegans, is a synthetic microRNA that is used for microRNA normalization in the recent studies, and in this section we summarize some of the research that normalized values using cel-miR-39. Miyoshi et al, 6 who reported miR-139-5p upregulation in the serum samples of recurrence-positive CRC patients, added 25 fmol of cel-miR-39 to each sample for data normalization. Likewise, Toiyama et al 7 added 25 fmol of cel-miR-39 to each sample to normalize C t values of serum miR-200c, which is a noninvasive biomarker for CRC prognosis.…”

Non‐invasive metastasis prognosis from plasma metabolites in stage II colorectal cancer patients: The DACHS study

“…Multiple genomics, transcriptomics and proteomics studies on discovery of prognostic markers in CRC patients had been performed. Here, we assessed the potential of metabolomics and plasma metabolic profiles in predicting metastasis in stage II CRC patients.…”