J 2017

Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis

PICHLER, M., V. STIEGELBAUER, Petra VYCHYTILOVÁ, C. IVAN, H. LING et. al.

Základní údaje

Originální název

Genome-Wide miRNA Analysis Identifies miR-188-3p as a Novel Prognostic Marker and Molecular Factor Involved in Colorectal Carcinogenesis

Autoři

PICHLER, M. (40 Rakousko), V. STIEGELBAUER (40 Rakousko), Petra VYCHYTILOVÁ (203 Česká republika, domácí), C. IVAN (40 Rakousko), H. LING (40 Rakousko), E. WINTER (40 Rakousko), X.N. ZHANG (840 Spojené státy), M. GOBLIRSCH (40 Rakousko), A. WULF-GOLDENBERG (276 Německo), M. OHTSUKA (840 Spojené státy), J. HAYBAECK (840 Spojené státy), M. SVOBODA (203 Česká republika), Y. OKUGAWA (840 Spojené státy), A. GERGER (840 Spojené státy), G. HOEFLER (40 Rakousko), A. GOEL (840 Spojené státy), Ondřej SLABÝ (203 Česká republika, garant, domácí) a G.A. CALIN (840 Spojené státy)

Vydání

Clinical cancer research, Philadelphia, AMER ASSOC CANCER RESEARCH, 2017, 1078-0432

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 10.199

Kód RIV

RIV/00216224:14740/17:00100443

Organizační jednotka

Středoevropský technologický institut

UT WoS

000396015600023

Klíčová slova anglicky

ANTI-EGFR THERAPY; TUMOR-GROWTH; COLON-CANCER; MICRORNA SIGNATURES; PREDICTIVE-VALUE; STAGE-II; METASTASIS; EXPRESSION; PROGRESSION; BIOMARKER

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 26. 4. 2021 13:41, Mgr. Tereza Miškechová

Anotace

V originále

Purpose: Characterization of colorectal cancer transcriptome by high-throughput techniques has enabled the discovery of several differentially expressed genes involving previously unreported miRNA abnormalities. Here, we followed a systematic approach on a global scale to identify miRNAs as clinical outcome predictors and further validated them in the clinical and experimental setting. Experimental Design: Genome-wide miRNA sequencing data of 228 colorectal cancer patients from The Cancer Genome Atlas dataset were analyzed as a screening cohort to identify miRNAs significantly associated with survival according to stringent pre-specified criteria. A panel of six miRNAs was further validated for their prognostic utility in a large independent validation cohort (n = 332). In situ hybridization and functional experiments in a panel of colorectal cancer cell lines and xenografts further clarified the role of clinical relevant miRNAs. Results: SixmiRNAs (miR-92b-3p, miR-188-3p, miR-221-5p, miR-331-3p, miR-425-3p, and miR-497-5p) were identified as strong predictors of survival in the screening cohort. High miR-188-3p expression proves to be an independent prognostic factor [screening cohort: HR = 4.137; 95% confidence interval (CI), 1.568-10.917; P = 0.004; validation cohort: HR = 1.538; 95% CI, 1.107-2.137; P = 0.010, respectively]. Forced miR-188-3p expression increased migratory behavior of colorectal cancer cells in vitro and metastases formation in vivo (P < 0.05). The promigratory role of miR-188-3p is mediated by direct interaction with MLLT4, a novel identified player involved in colorectal cancer cell migration. Conclusions: miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. (C) 2016 AACR.

Návaznosti

ED1.1.00/02.0068, projekt VaV
Název: CEITEC - central european institute of technology
90004, velká výzkumná infrastruktura
Název: BBMRI-CZ