It is well known that
microRNAs (miRs) are abnormally expressed in various
cancers and target the messenger RNAs (mRNAs) of
cancer-associated genes. While (miRs) are abnormally expressed in various
cancers, whether miRs directly target oncogenic
proteins is unknown. The present study investigated the inhibitory effects of miR-18a on
colon cancer progression, which was considered to be mediated through its direct binding and degradation of
heterogeneous nuclear ribonucleoprotein A1 (
hnRNP A1). An MTT assay and xenograft model demonstrated that the transfection of miR-18a induced apoptosis in SW620 cells. A binding assay revealed direct binding between miR-18a and
hnRNP A1 in the cytoplasm of SW620 cells, which inhibited the oncogenic functions of
hnRNP A1. A competitor
RNA, which included the complementary sequence of the region of the miR-18a-hnRNP A1 binding site, repressed the effects of miR-18a on the induction of
cancer cell apoptosis. In vitro single and in vivo double
isotope assays demonstrated that miR-18a induced the degradation of
hnRNP A1. An immunocytochemical study of
hnRNP A1 and LC3-II and the inhibition of autophagy by
3-methyladenine and ATG7, p62 and BAG3
siRNA showed that miR-18a and
hnRNP A1 formed a complex that was degraded through the autophagolysosomal pathway. This is the first report showing a novel function of a miR in the autophagolysosomal degradation of an oncogenic
protein resulting from the creation of a complex consisting of the miR and a
RNA-binding protein, which suppressed
cancer progression.