D 2008

Significance of microRNA-21 in colorectal cancer pathogenesis.

SLABÝ, Ondřej, Roman HRSTKA, Lenka DUBSKÁ, Marek SVOBODA, Eva RŮČKOVÁ et. al.

Basic information

Original name

Significance of microRNA-21 in colorectal cancer pathogenesis.

Name in Czech

Significance of microRNA-21 in colorectal cancer pathogenesis.

Authors

SLABÝ, Ondřej (203 Czech Republic, guarantor), Roman HRSTKA (203 Czech Republic), Lenka DUBSKÁ (203 Czech Republic), Marek SVOBODA (203 Czech Republic), Eva RŮČKOVÁ (203 Czech Republic), Jaroslava OVESNÁ (203 Czech Republic) and Rostislav VYZULA (203 Czech Republic)

Edition

2008, 275, Suppl. 1. Oxford, UK, FEBS Journal, p. 465-465, 1 pp. 2008

Publisher

FEBS

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.139

RIV identification code

RIV/00216224:14110/08:00028239

Organization unit

Faculty of Medicine

ISSN

UT WoS

000256633301661

Keywords in English

colorectal; microRNAs

Tags

International impact, Reviewed
Změněno: 30/9/2008 09:03, prof. RNDr. Ondřej Slabý, Ph.D.

Abstract

V originále

MicroRNAs (miRNAs) are endogenously expressed short non-coding 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). In our study, we examined by Real-Time PCR expression levels of microRNA-21 (miR-21) in tumors of 29 colorectal cancer patients. For 6 cases of CRC samples also adjacent non-tumor tissues were analyzed. 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. Expression levels of miR-21 were significantly higher in tumors comparing to normal mucosa (p = 0,0001). High expression of miR-21 was also associated with lymph node positivity (p = 0,025) and the development of distant metastases (p = 0,009) in CRC patients. To elucidate function of miR-21 in colon cancer cells (DLD1, SW837, HCT116) we tested effects of synthetic 2'OMe-anti-sense-miR-21 (anti-miR-21) transfection (2'OMe-EGFP as control) on their proliferation, cell cycle regulation, sensitization to chemotherapeutic agents (5-fluorouracil, irinotecan, oxaliplatin) and invasive properties. We observed 15-30% decrease of cells proliferation by MTT test after transfection of anti-miR-21 in comparison with control cells. Moreover, cytostatic effect of treatments was enhanced about 20-30% in transfected colon cancer cells. Interestingly, these actions of anti-miR-21 were not associated with significant changes of cell cycle. We hypothesize, that miR-21 affects directly proliferation and now we are testing common markers of proliferation (Ki-67) and those which are possibly under miR-21 post-transcriptional control. Simultaneously, we evaluate changes in invasive properties of anti-miR-21 transfected cancer cells by matrigel invasion assay. Our results suggest possible role of miR-21 in colorectal cancer pathogenesis. Supported by IGA MZ CR NR/9076-4 and project MZ0MOU2005

In Czech

MicroRNAs (miRNAs) are endogenously expressed short non-coding 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). In our study, we examined by Real-Time PCR expression levels of microRNA-21 (miR-21) in tumors of 29 colorectal cancer patients. For 6 cases of CRC samples also adjacent non-tumor tissues were analyzed. 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. Expression levels of miR-21 were significantly higher in tumors comparing to normal mucosa (p = 0,0001). High expression of miR-21 was also associated with lymph node positivity (p = 0,025) and the development of distant metastases (p = 0,009) in CRC patients. To elucidate function of miR-21 in colon cancer cells (DLD1, SW837, HCT116) we tested effects of synthetic 2'OMe-anti-sense-miR-21 (anti-miR-21) transfection (2'OMe-EGFP as control) on their proliferation, cell cycle regulation, sensitization to chemotherapeutic agents (5-fluorouracil, irinotecan, oxaliplatin) and invasive properties. We observed 15-30% decrease of cells proliferation by MTT test after transfection of anti-miR-21 in comparison with control cells. Moreover, cytostatic effect of treatments was enhanced about 20-30% in transfected colon cancer cells. Interestingly, these actions of anti-miR-21 were not associated with significant changes of cell cycle. We hypothesize, that miR-21 affects directly proliferation and now we are testing common markers of proliferation (Ki-67) and those which are possibly under miR-21 post-transcriptional control. Simultaneously, we evaluate changes in invasive properties of anti-miR-21 transfected cancer cells by matrigel invasion assay. Our results suggest possible role of miR-21 in colorectal cancer pathogenesis. Supported by IGA MZ CR NR/9076-4 and project MZ0MOU2005

Links

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