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.; V. STIEGELBAUER; Petra VYCHYTILOVÁ ORCID; C. IVAN; H. LING; E. WINTER; X.N. ZHANG; M. GOBLIRSCH; A. WULF-GOLDENBERG; M. OHTSUKA; J. HAYBAECK; M. SVOBODA; Y. OKUGAWA; A. GERGER; G. HOEFLER; A. GOEL; Ondřej SLABÝ a G.A. CALIN
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
EID Scopus
2-s2.0-85014729382
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 |
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| 90004, velká výzkumná infrastruktura |
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