TY - JOUR
AU1 - Zhao, Ping
AU2 - Ma, Yu-guang
AU3 - Zhao, Yang
AU4 - Liu, Di
AU5 - Dai, Zhi-jun
AU6 - Yan, Chang-you
AU7 - Guan, Hai-tao
AB - Objective Although DNA-mismatch-repair-deficient (dMMR) status and aberrant expression of miRNAs are both critically implicated in the pathogenesis of resistance to 5-fluorouracil (5-FU) in colorectal cancer (CRC), whether these two factors regulate tumor response to 5-FU in a coordinated manner remains unknown. This study is designed to elucidate whether changes in miR-552 expression levels correlate to 5-FU-based chemoresistance in CRC, and to further identify the putative targets of miR-552 using multiple approaches. Methods miR-552 expression was assessed in 5-FU-resistant CRC tissues and cells using real-time PCR. Ee ff cts of miR-552 dysregulation on 5-FU resistance in CRC cells were determined by measuring cell viability, apoptosis and in vivo oncogenic capacity. Finally, we studied the posttranscriptional regulation of SMAD2 by miR-552 using multiple approaches including luciferase reporter assay, site-directed mutagenesis and transient/stable transfection, at molecular and functional levels. Results Expression of miR-552 was significantly downregulated in 5-FU-resistant CRC tissues and cells, and this down- regulation, regulated by dMMR, was associated with poor postchemotherapy prognosis. Functionally, forced expression of miR-552 exhibited a proapoptotic effect and attenuated 5-FU resistance, whereas inhibition of miR-552 expression potenti- ated 5-FU resistance in CRC cells. Mechanically, miR-552 directly targeted the 3′-UTR of SMAD2, and stable ablation of SMAD2 
TI - MicroRNA-552 deficiency mediates 5-fluorouracil resistance by targeting SMAD2 signaling in DNA-mismatch-repair-deficient colorectal cancer
JF - Cancer Chemotherapy and Pharmacology
DO - 10.1007/s00280-019-03866-7
DA - 2019-05-13
UR - https://www.deepdyve.com/lp/springer-journals/microrna-552-deficiency-mediates-5-fluorouracil-resistance-by-x0rEsYeaHi
SP - 427
EP - 439
VL - 84
IS - 2
DP - DeepDyve
ER -