J 2007

Association of miR-21, miR-31, miR-143, miR-145 and let-7a-1 levels with histopathologic features of colorectal cancer

SLABÝ, Ondřej, Marek SVOBODA, Pavel FABIAN, Miroslav SVOBODA, Ingrid GARAJOVÁ et. al.

Basic information

Original name

Association of miR-21, miR-31, miR-143, miR-145 and let-7a-1 levels with histopathologic features of colorectal cancer

Name in Czech

Association of miR-21, miR-31, miR-143, miR-145 and let-7a-1 levels with histopathologic features of colorectal cancer

Authors

SLABÝ, Ondřej (203 Czech Republic), Marek SVOBODA (203 Czech Republic), Pavel FABIAN (203 Czech Republic), Miroslav SVOBODA (203 Czech Republic), Ingrid GARAJOVÁ (703 Slovakia), Milana ŠACHLOVÁ (203 Czech Republic), Tamara ŠMERDOVÁ (203 Czech Republic), Dana KNOFLÍČKOVÁ (203 Czech Republic) and Rostislav VYZULA (203 Czech Republic, guarantor)

Edition

European Journal of Cancer, 2007, 0959-8049

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.454

RIV identification code

RIV/00216224:14110/07:00019108

Organization unit

Faculty of Medicine

UT WoS

000250204000249

Keywords in English

colorectal cancer; microRNA; pathogenesis; metastasis

Tags

International impact, Reviewed
Změněno: 19/1/2008 15:34, prof. RNDr. Ondřej Slabý, Ph.D.

Abstract

V originále

RNAs, that repress protein translation through binding to target mRNAs. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. Previous studies, mainly based on microarrays technology applied on colorectal cancer cell lines, showed altered expression levels of several miRNAs in colorectal cancer (CRC). MATERIALS AND METHODS: In our study, we examined by Real-Time PCR expression levels of miR-21, miR-31, miR-143, miR-145 and let-7a-1 in bioptic samples of 29 colorectal cancer patients including 3 cases of IUCC Stage I, 11 of Stage II, 6 of Stage III, 9 of Stage IV. For 6 cases of CRC samples also adjacent non-tumor tissues were analyzed. MiRNAs expression levels were correlated with tumor stage, grade, size, anatomical localization, serum CEA levels and p53 protein expression in tumors. For data normalization we tried different approaches (18S rRNA, GAPDH, let-7a-1). Finally, variability of let-7a-1 expression was shown to be the lowest. P values were calculated using Mann-Whitney U test. RESULTS: Expression levels of all analyzed miRNAs significantly differ in tumor and normal mucosa, miR-21 (p=0,0001) and miR-31 (p=0,0006) were up-regulated and miR-143 (p=0,013) and miR-145 (p=0,018) were down-regulated in tumors. MiR-21 was also correlated with CRC stage. Although the highest levels of miR-143 and miR-145 were in normal mucosa, we identified positive correlation of tumor stage and their expression suggesting altered tumor suppressor function of these miRNAs in early events of colorectal carcinogenesis. Distal CRC showed significant up-regulation of miR-31 (p=0,024) expression. Higher serum levels of CEA were associated with down-regulation of miR-145 (p=0,05). Tumors with high expression of p53 protein had significantly lower expression of miR-143 (p=0,02). We have not associated any of studied miRNAs to tumor grade and tumor size. Tumors with down-regulated miR-143 and miR-145 were bigger and more frequent (not significantly) in proximal colon. CONCLUSIONS: Our results suggest possible roles of miR-21, miR-31, miR-143 and miR-145 in colorectal cancer pathogenesis and different histopathologic phenotypes. Supported by IGA MZ CR NR/9076 - 4

In Czech

Association of miR-21, miR-31, miR-143, miR-145 and let-7a-1 levels with histopathologic features of colorectal cancer

Links

NR9076, research and development project
Name: Genomické profilování v predikci odpovědi na chemoradioterapii u pacientů s lokálně pokročilým karcinomem konečníku