MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

Theranostics
Xin LaiJulio Vera

Abstract

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this coopera...Continue Reading

Citations

Nov 20, 2019·Expert Opinion on Drug Discovery·Kenneth K W ToWilliam C S Cho
May 26, 2018·Briefings in Bioinformatics·Tingting ShaoYongsheng Li
Aug 29, 2020·Cells·Neeraj ChauhanMurali M Yallapu
Feb 6, 2020·International Journal of Molecular Sciences·Elena MatveishinaYulia A Medvedeva
Jan 13, 2021·International Journal of Molecular Sciences·Julio VeraMartin Eberhardt
Dec 31, 2020·International Journal of Molecular Sciences·Ilaria PlantamuraMarilena V Iorio
Dec 18, 2020·Frontiers in Oncology·Simona Ruxandra VolovatIolanda Augustin
Aug 20, 2021·Journal of Orthopaedic Surgery and Research·Yumei BaiYumei Zhang
Jul 4, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ni SunXiao-Ji Lin

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Methods Mentioned

BETA
transfection
PCR
MDS
fluorescence microscopy

Software Mentioned

BIOVIA
BIOVIA ® Discovery Studio
MATLAB
CompuSyn
NUPACK
miRanda
RNAComposer
VARNA
mfe

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