microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression

Experimental & Molecular Medicine
Heejin LeeEun Kyung Lee

Abstract

Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, th...Continue Reading

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Citations

Apr 4, 2019·Journal of Cellular Physiology·Wei FengShaoqing Ju
Jul 10, 2019·Current Drug Targets·Seyed Mostafa ParizadehAmir Avan
Jun 21, 2019·MicroRNA·Ioannis A ZiogasGeorgios Tsoulfas
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Jan 12, 2021·International Immunopharmacology·Mohammad Reza Mohammad Hoseini AzarSiamak Sandoghchian Shotorbani
Nov 12, 2020·International Journal of Molecular Sciences·Kyoko OuraTsutomu Masaki
Sep 20, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Metin ÇalışkanVildan Bozok Çetintaş

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Methods Mentioned

BETA
PCR
fluorescence-activated cell-sorting
flow cytometry
electrophoresis
FACS
transfection
ubiquitination

Software Mentioned

miRDB
PANTHER
miRWalk
Targetscan
ImageJ

Related Concepts

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