E2F8, a direct target of miR-144, promotes papillary thyroid cancer progression via regulating cell cycle

Background: Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2 Gamma 8, a novel identified E2 Gamma family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. Methods: E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients. The effects of E2F8 and miR-144 on proliferation were evaluated both in vitro and in vivo. Luciferase reporter assay was used to determine E2F8 was a direct target of miR-144. Results: E2F8 was widely upregulated in PTC tissues, and overexpression of E2F8 was correlated with more aggressive clinicopathological features. In contrast, we found that silence of E2F8 significantly suppressed proliferation of PTC cells by inducing G1-phase arrest via downregulating Cyclin D1 (CCND1) both in vitro and in vivo. We also identified miR-144 as a tumor-suppressive microRNA that directly targeted E2F8 to inhibit proliferation of PTC cells in vitro and in vivo. Moreover, miR-144 was widely downregulated in PTC, where its expression correlated inversely with E2F8 expression. Conclusions: Our results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy.