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The Bioactivity of D-/L-Isonucleoside- and 2'-Deoxyinosine-Incorporated Aptamer AS1411s Including DNA Replication/MicroRNA Expression.

Abstract：

:In this study, chemical modification of 2'-deoxyinosine (2'-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement. They stabilized the G-quadruplex, remained highly resistant to serum degradation and specificity for nucleolin, further inhibited tumor cell growth, exhibited a stronger ability to influence the different phases of the tumor cell cycle, induced S-phase arrest, promoted the inhibition of DNA replication, and suppressed the unwound function of a large T antigen as powerful as AS1411. The microarray analysis and TaqMan PCR results showed that FCL-II can upregulate the expression of four breast-cancer-related, lowly expressed miRNAs and downregulate the expression of three breast-cancer-related, highly expressed miRNAs (>2.5-fold). FCL-II resulted in enhanced treatment effects greater than AS1411 in animal experiments (p < 0.01). The computational results further proved that FCL-II exhibits more structural advantages than AS1411 for binding to the target protein nucleolin, indicating its great potential in antitumor therapy.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Fan X,Sun L,Li K,Yang X,Cai B,Zhang Y,Zhu Y,Ma Y,Guan Z,Wu Y,Zhang L,Yang Z

doi

10.1016/j.omtn.2017.09.010

subject

Has Abstract

pub_date

2017-12-15 00:00:00

pages

218-229

issn

2162-2531

pii

S2162-2531(17)30260-3

journal_volume

9

pub_type

杂志文章

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