Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer

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Abstract

Epithelial-mesenchymal transition (EMT) is an early and key process in the metastatic cascade during the progression of colorectal cancer (CRC). The aim of the present study was to identify deregulated EMT-related microRNAs (miRNAs/miRs) of CRC and assess the effect of differentially expressed miRNAs on the prognosis of patients with CRC. Genome-wide expression profiling of miRNAs was assessed in 3 EMT-negative and 3 EMT-positive CRC tissues. Differentially expressed miRNA was further validated in 90 pairs of CRC and corresponding paracarcinoma tissues using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 6 miRNAs (miR-10a-5p miR-204-3p, miR-1224-3p, miR-193a-3p, miR-365a-3p and miR-3678-3p) were identified to be differentially expressed between different EMT statuses of CRC tissues. Following validation using RT-qPCR, 3 miRNAs (miR-10a-5p, miR-365a-3p and miR-193a-3p) were selected for subsequent studies. The expression levels of miR-10a-5p, miR-193a-3p and miR-365a-3p were markedly increased compared with levels in corresponding paracarcinoma tissues. Survival analyses revealed that down-regulation of miR-193a-3p was associated with worse prognosis of patients with CRC, particularly in female and older patients. The results of the present study indicate that miR-193a-3p may be an EMT-related biomarker and serve as a novel prognostic factor for CRC.

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Diagnostic and prognostic microRNAs in stage II colon cancer.

Troels Schepeler, Jørgen T Reinert, Marie Ostenfeld … (2008)

MicroRNAs (miRNA) are a class of small noncoding RNAs with important posttranscriptional regulatory functions. Recent data suggest that miRNAs are aberrantly expressed in many human cancers and that they may play significant roles in carcinogenesis. Here, we used microarrays to profile the expression of 315 human miRNAs in 10 normal mucosa samples and 49 stage II colon cancers differing with regard to microsatellite status and recurrence of disease. Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue. Microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles. Furthermore, a biomarker based on miRNA expression profiles could predict recurrence of disease with an overall performance accuracy of 81%, indicating a potential role of miRNAs in determining tumor aggressiveness. The expression levels of miR-320 and miR-498, both included in the predictive biomarker, correlated with the probability of recurrence-free survival by multivariate analysis. We successfully verified the expression of selected miRNAs using real-time reverse transcription-PCR assays for mature miRNAs, whereas in situ hybridization was used to detect the accumulation of miR-145 and miR-320 in normal epithelial cells and adenocarcinoma cells. Functional studies showed that miR-145 potently suppressed growth of three different colon carcinoma cell lines. In conclusion, our results suggest that perturbed expression of numerous miRNAs in colon cancer may have a functional effect on tumor cell behavior, and, furthermore, that some miRNAs with prognostic potential could be of clinical importance.

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Epigenetic regulation of microRNA expression in colorectal cancer.

Eva Bandres, Xabier Agirre, Nerea Bitarte … (2009)

In the last years, microRNAs (miRNA) have emerged as new molecular players involved in carcinogenesis. Deregulation of miRNAs expression has been shown in different human cancer but the molecular mechanism underlying the alteration of miRNA expression is unknown. To identify tumor-supressor miRNAs silenced through aberrant epigenetic events in colorectal cancer (CRC), we used a sequential approach. We first identified 5 miRNAs down-regulated in patient with colorectal cancer samples and located around/on a CpG island. Treatment with a DNA methyltransferase inhibitor and a HDAC inhibitor restored expression of 3 of the 5 microRNAs (hsa-miR-9, hsa-miR-129 and hsa-miR-137) in 3 CRC cell lines. Expression of hsa-miR-9 was inversely correlated with methylation of their promoter regions as measure by MSP and bisulphate sequencing. Further, methylation of the hsa-miR-9-1, hsa-miR-129-2 and hsa-miR-137 CpG islands were frequently observed in CRC cell lines and in primary CRC tumors, but not in normal colonic mucosa. Finally, methylation of hsa-miR-9-1 was associated with the presence of lymph node metastasis. In summary, our results aid in the understanding of miRNA gene regulation showing that aberrant DNA methylation and histone modifications work together to induce silencing of miRNAs in CRC.

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Genetics, diagnosis and management of colorectal cancer (Review)

Marina De Rosa, UGO PACE, DANIELA REGA … (2015)

Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. Surgery represents the mainstay of treatment in early cases but often patients are primarily diagnosed in an advanced stage of disease and sometimes also distant metastases are present. Neoadjuvant therapy is therefore needed but drug resistance may influence response and concur to recurrent disease. At molecular level, it is a very heterogeneous group of diseases with about 30% of hereditary or familial cases. During colorectal adenocarcinomas development, epithelial cells from gastrointestinal trait acquire sequential genetic and epigenetic mutations in specific oncogenes and/or tumour suppressor genes, causing CRC onset, progression and metastasis. Molecular characterization of cancer associated mutations gives valuable information about disease prognosis and response to the therapy. Very early diagnosis and personalized care, as well as a better knowledge of molecular basis of its onset and progression, are therefore crucial to obtain a cure of CRC. In this review, we describe updated genetics, current diagnosis and management of CRC pointing out the extreme need for a multidisciplinary approach to achieve the best results in patient outcomes.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Lett

Journal ID (iso-abbrev): Oncol Lett

Journal ID (publisher-id): OL

Title: Oncology Letters

Publisher: D.A. Spandidos

ISSN (Print): 1792-1074

ISSN (Electronic): 1792-1082

Publication date (Print): July 2017

Publication date (Electronic): 26 May 2017

Publication date PMC-release: 26 May 2017

Volume: 14

Issue: 1

Pages: 1061-1067

Affiliations

[1 ]Department of Gastroenterology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China

[2 ]Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China

[3 ]Department of Pathology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China

[4 ]CMC Biobank and Translational Medicine Institute, Taizhou, Jiangsu 225312, P.R. China

[5 ]National Engineering Center for Biochip at Shanghai, Shanghai 201203, P.R. China

[6 ]Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China

Author notes

Correspondence to: Dr Junxing Huang, Department of Oncology, Taizhou People's Hospital, 210 Yingchun Road, Taizhou, Jiangsu 225300, P.R. China, E-mail: hjxtz@ 123456sina.cn

Dr Hengjun Gao, Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, P.R. China, E-mail: hengjun_gao@ 123456shbiochip.com

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Publisher ID: OL-0-0-6266

DOI: 10.3892/ol.2017.6266

PMC ID: 5494605

PubMed ID: 28693274

SO-VID: 3fe61bbb-6679-49fe-a598-2e9df5ca51ac

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Decreased expression of miR-193a-3p is associated with poor prognosis in colorectal cancer

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Karger: Oncology

Most cited references 21

Diagnostic and prognostic microRNAs in stage II colon cancer.

Epigenetic regulation of microRNA expression in colorectal cancer.

Genetics, diagnosis and management of colorectal cancer (Review)

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