A circular RNA derived from FAT atypical cadherin 3 promotes lung cancer progression via forming a regulatory loop with oncogenic ELAV like RNA binding protein 1

Abstract

Circular RNA (circRNA) is a covalently closed endogenous RNA that participates in disease progression. However, its role in lung cancer is largely undetermined. In the present study, we found an onctogenic circRNA in lung cancer, FAT atypical cadherin 3 (FAT3) circRNA (circ-FAT3) was remarkably upregulated in lung cancer in comparison to paired normal tissues. High circ-FAT3 was closely linked to larger tumour size, lymph node metastasis, later clinical stage, as well as dismal outcome. Stable knockdown of circ-FAT3 inhibited cell proliferation and metastasis both in vitro and in vivo. RNA binding protein ELAV like RNA binding protein 1 (HuR) was found to bind to introns flanking circ-FAT3, promoting the cyclization and generation of circ-FAT3. Further, circ-FAT3 was able to sponge miR-136-5p by acting as a competing endogenous RNA (ceRNA), alleviating the repressive effect of miR-136-5p on HuR mRNA at the transcriptional and post-transcriptional levels. Moreover, circ-FAT3 expression in lung cancer tissues was strongly positively and negatively correlated with HuR and miR-136-5p expression, respectively. Overall, our data reveal the previously uncharacterized regulatory loop of circ-FAT3/miR-136-5p/HuR in lung cancer and provide novel evidence for the importance of circRNA as a ceRNA in tumorigenesis.