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

Abstract

BackgroundThyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown.MethodsE2F8 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.ResultsE2F8 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.ConclusionsOur results demonstrate a new miR-144/E2F8/CCND1 regulatory axis controlling PTC development, which may offer a potential prognostic and therapeutic strategy.Trial registrationNo applicable.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0504-6) contains supplementary material, which is available to authorized users.

Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor‐β type I receptor/apoptosis signal‐regulating kinase 1/mitogen‐activated protein kinase signaling axis

“…Therefore, clarifying the mechanism concerning the dysregulation of cell cycle regulator will be of great importance. Sun et al previously demonstrated a new miR‐144/E2F8/Cyclin D1 regulatory axis controlling PTC development . Here, we proved that SLC35F2 could regulate cell cycle progression by accelerating G1/S phase transition without affecting apoptosis of PTC cells, suggesting that SLC35F2 may be a novel modulator of the cell cycle.…”

HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

“…Recent studies have demonstrated that transcription factors were involved in the expression of miRNAs . Transcription factor E2F8, was reported in the progression of several human cancers, such as ovarian, hepatocellular, lung and breast cancers .…”

“…Recent studies have demonstrated that transcription factors were involved in the expression of miRNAs. 48 Transcription factor E2F8, was reported in the progression of several human cancers, such as ovarian, hepatocellular, lung and breast cancers. [49][50][51][52] We performed the luciferase reporter assay to test the binding of miR130a, miR-130b or miR-19 with HOXD-AS1 and E2F8; our results showed that among these miRNAs, miR-130a could simultaneously binds to HOXD-AS1 and E2F8.…”

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

“…E2F7 is involved in regulating the cell cycle and its highest expression occurs at the S-phase of the cell cycle [130]. E2F7 is aberrantly overexpressed in the CSCs of HCC, and promotes stem cell proliferation and tumorsphere formation not only through regulating the cell cycle but also activating the Akt/β-catenin/cyclin D1 pathway.…”