ncRNA basic information
ncRNA ID:
MI0000681
ncRNA Database:
miRBase
ncRNA Name:
miR-155
ncRNA Type:
miRNA
ncRNA Expression:
up-regulated
ncRNA Method:
RT-qPCR
ncRNA Target Gene:
WEE1
ncRNA Pathway:
NA
Evidence (ncRNA-drug):
validated
drug basic information
Drug ID:
DB00541 (APRD00495)
Drug Name:
Vincristine
Drug Method:
The purpose of the present study was to investigate microRNA (miRNA) involvement in vincristine resistance in DLBCL, which was pursued by functional in vitro analysis in DLBCL cell lines and by outcome analysis of patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Differential miRNA expression analysis identified miR-155 as highly expressed in vincristine-sensitive DLBCL cell lines compared with resistant ones. Ectopic upregulation of miR-155 sensitized germinal-center B-cell-like (GCB)-DLBCL cell lines to vincristine, and consistently, reduction and knockout of miR-155 induced vincristine resistance, documenting that miR-155 functionally induces vincristine sensitivity. Target gene analysis identified miR-155 as inversely correlated with Wee1, supporting Wee1 as a target of miR-155 in DLBCL. Chemical inhibition of Wee1 sensitized GCB cells to vincristine, suggesting that miR-155 controls vincristine response through Wee1. Outcome analysis in clinical cohorts of DLBCL revealed that high miR-155 expression level was significantly associated with superior survival for R-CHOP-treated patients of the GCB subclass, independent of international prognostic index, challenging the commonly accepted perception of miR-155 as an oncomiR. However, miR-155 did not provide prognostic information when analyzing the entire DLBCL cohort or activated B-cell-like classified patients.
Drug Response:
sensitive
Cancer basic information
Cancer:
diffuse large B-cell lymphoma
Tissue/Cell:
cell line(SU-DHL-5, OCI-Ly7)
Other information
Title:
MicroRNA-155 controls vincristine sensitivity and predicts superior clinical outcome in diffuse large B-cell lymphoma.
Journal:
Blood Adv
Published:
2019
PubMed ID:
30967394