MicroRNAs (
miRNAs) are involved in
cancer progression via translational degradation in a sequence-specific manner of the 3'-untranslated region (
3'UTR) of
messenger RNA (
mRNA). The involvement of
miRNA in the biological progression of various
cancer types is considered to be a potential target.
Primary miRNA (
pri-miRNA) and precursor-
miRNA (
pre-miRNA) synthesize the
miRNA by dicer-catalyzed processes thus targeting pri/
pre-miRNA by
phytochemicals is amongst the appropriate approaches for anticancer
therapies.
Flavonoids category of
phytochemicals is well-known for its chemotherapeutic and chemopreventive potential against multiple
cancer types. However, the molecular interactions of
flavonoids with
miRNAs are not reported so far. Thus, this study aims to identify the promising
flavonoids as the antagonist of
miRNAs (pre-miR21, pri-miR-208a, pri-miR-378a, pri-miR320b, pri-miR-300, pri-miR-19b, and pre-miR-20b) using molecular docking simulations studies. Among the tested
flavonoids,
narirutin showed highest binding energy (-11.7 kcal/mol) against pri-miR19b followed by pri-miR-378a (-11.4 kcal/mol) > pri-miR320b (-11.2 kcal/mol) = pri-miR-300 (-11.2 kcal/mol) > pri-miR-208a (-9.0 kcal/mol) > pre-miR-20b (- 8.3 kcal/mol). The molecular dynamic simulation experiment confirmed that
narirutin destabilizes the tertiary structure of
pri-miRNA in comparison to apo-
RNA. The finding indicates that
narirutin binding with
pre-miRNA causes disruption of pri-
RNA structure that creates a loss of DICER-
pre-miRNA interactions by hindering the
pre-miRNA synthesis, thereby affecting
miRNA processing. Further pharmacokinetics and toxicity prediction revealed that it is non-carcinogenic, non-mutagenic, and does not inhibit the CYPs activity. Thus,
narirutin could be a possible antagonist of oncogenic
miRNAs, therefore could be useful for
miRNA-targeted
cancer prevention and treatment.