miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1

Varování

Publikace nespadá pod Fakultu sportovních studií, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	MRÁZ Marek CHEN L.G. RASSENTI L.Z. GHIA E.M. LI H.Y. JEPSEN K. SMITH E.N. MESSER K. FRAZER K.A. KIPPS T.J.
Rok publikování	2014
Druh	Článek v odborném periodiku
Časopis / Zdroj	Blood
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	http://www.bloodjournal.org/content/124/1/84
Doi	http://dx.doi.org/10.1182/blood-2013-09-527234
Obor	Onkologie a hematologie
Klíčová slova	GENE MUTATION STATUS; DOWN-REGULATION; C-MYB; DISEASE PROGRESSION; PROTEIN EXPRESSION; CD38 EXPRESSION; CLL PATIENTS; MICRORNAS; ZAP-70; APOPTOSIS
Popis	We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia cell expression levels that varied among patients. CLL cells that expressed zeta-chain-associated protein of 70 kDa (ZAP-70) or that used unmutated immunoglobulin heavy chain variable (IGHV) genes, each had a median expression level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV genes. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3' untranslated regions having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that enhance B-cell receptor signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 was a significant independent predictor of longer treatment-free survival or overall survival, whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for overall survival. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor, thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
Související projekty:	Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci