HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6
Menghui Yin,
Meidie Cheng,
Chengli Liu,
Keli Wu,
Wei Xiong,
Ji Fang,
Yinxiong Li,
Biliang Zhang
Affiliations
Menghui Yin
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author .
Meidie Cheng
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China
Chengli Liu
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China
Keli Wu
School of Life Science, University of Science and Technology of China, Hefei 230026, China
Wei Xiong
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China
Ji Fang
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China
Yinxiong Li
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Public Health, Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Biliang Zhang
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Guangzhou, Guangdong 510530, China; Corresponding author
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.
