<b>DEC1 promotes hypoxia-induced epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma </b><b>cells </b>

Abstract

Differentiated embryonic chondrocyte (DEC) 1 has been reported to be involved in cell differentiation, hypoxia response, and cancer progression. Recent studies have demonstrated that hypoxiainducible factor (HIF)-1α induces epithelial-mesenchymal transition (EMT) in carcinoma cells to facilitate cell invasiveness and metastasis. However, it remains unclear whether DEC1 participates in hypoxia-mediated EMT processes. In the present study, we reported that hypoxia induced DEC1 expression in hepatocellular carcinoma (HCC) HepG2 cells, and DEC1 negatively regulated expression of HIF-1α and E-cadherin in transcriptional/translational levels. Cell morphological changes were evaluated with hematoxylin and eosin (H-E) staining. Exposure to hypoxia caused spindle-like shape in some of the HepG2 cells, and DEC1 overexpression furthered these changes. In conclusions, DEC1 is involved in hypoxia-induced EMT processes via negatively regulating E-cadherin expression in HepG2 cells.There has been a great discussion about the relation between hypoxia and epithelial-mesenchymal transition (EMT). Intratumoral hypoxia followed by stabilization of hypoxia-inducible factor (HIF)-1α promotes acquisition of EMT-like features in various kinds of carcinomas (2, 9, 11, 18) as well as hematopoietic tumors (1). Several studies have reported that HIF-1α overexpression is positively correlated with EMT induction in hepatocellular carcinoma (HCC) cell lines and surgical resection specimens (7,8,20). In addition, hypoxia-induced EMT resulted in multidrug resistance in HCC cells (16), tumor metastasis after transcatheter arterial embolization (TAE) (4), and poor prognosis in HCC patients (6). It has been shown that curcumin, a botanical agent derived from the dried rhizome of Curcuma longa, eliminates the accumulation of HIF-1α to reduce the invasive potential of HepG2 cells (3). These findings indicated that hypoxia-induced EMT may be a significant prognosis marker and a crucial therapy target of HCC patients. Differentiated embryonic chondrocyte expressed gene (DEC) 1 (BHLHE40/Stra13/Sharp2) has been found as a transcriptional factor promoting the differentiation of chondrocytes (15) and regulating the circadian rhythm via suppressing CLOCK/BMAL1-enhanced promoter activity (5). Recently, DEC1 has been reported to be located on the downstream of HIF-1α pathway and the activation of HIF-1α and DEC1 causes tumor progression, invasion, and metastasis (13). Our previous studies have shown that DEC1 promotes TGF-β-induced EMT of pancreatic adenocarcinoma PANC-1 cells through Smad3 phosphorylation (17). However, the relation between DEC1 and hypoxia-induced EMT has not been reported in any human cancer cell lines. This study was undertaken to examine the relation between DEC1 and hypoxia-induced EMT in human HCC HepG2 cells.

MicroRNA‑153 suppresses human laryngeal squamous cell carcinoma migration and invasion by targeting the SNAI1 gene

“…This method can be extended to the interaction of other associated genes. Previous studies indicated that EMT markers are associated with human tumor metastasis ( 44 – 46 ). In the present study, only the association between miR-153 and SNAI1 in LSCC cells was analyzed.…”

Non-circadian aspects of BHLHE40 cellular function in cancer

“…Further, overexpression of BHLHE40 antagonized apoptosis induced by 8-MOP by abolishing the decrease of survivin and the activation of caspase-3 [134]. Hypoxia-induced BHLHE40 promoted EMT and induced metastasis in HepG2 cells [135,136]. Subsequent II receptor (R2), which recruits and phosphorylates a type I receptor (R1).…”

Calpain inhibition attenuates bleomycin-induced pulmonary fibrosis via switching the development of epithelial-mesenchymal transition

“…Differentiated embryonic chondrocyte-expressed gene 1 (DEC1), also called STRA13 in mouse and SHARP2 in rat, is a bHLH transcription factor that is involved in the regulation of cell growth and differentiation (Qian et al 2012 ; Rossner et al 1997 ). It has been reported that DEC1 played an important role in the regulation of the EMT in hepatocellular carcinoma (Murakami et al 2017 ). Loss of DEC1 expression is an early event in the development of lung cancer (Giatromanolaki et al 2003 ).…”