HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6

Abstract

Summary: The functional inactivation of tumor suppressor microRNA (miRNA) is closely related to the tumorigenesis of cancer. There are instances where the miRNA and the corresponding target both exist in a cell, but the target gene silencing do not occur as expected. Herein, we found that both miR-506 and its target CDK6 are highly co-expressed in lung cancer cells. Sequence analyses suggested that a miR-506 binding site (1648–1654) and a cis-element (1785–1795) for binding by heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) are evolutionarily conserved and forms a stem structure in the 3′ untranslated region (3′UTR) of CDK6. Furthermore, HNRNPA2B1 can bind to the stem structure to denature it and recruit the RNA helicase DExH-box helicase 9 (DHX9) to the 3′UTR, which ultimately facilitates miRNAs-mediated CDK6 silencing. These results indicate that the cis-element of the 3′UTR of CDK6, where HNRNPA2B1 binds, serves as an RNA switch to regulate miRNAs’ function in cancer cells.

Keywords

• Biological sciences
• Biochemistry
• Molecular biology
• Cell biology