Basic helix-loop-helix transcription factor DEC2 functions as an anti-apoptotic factor during paclitaxel-induced apoptosis in human prostate cancer cells

Abstract

The functions of basic helix-loop-helix (bHLH) transcription factor-differentiated embryonic chondrocyte (DEC)1 (BHLHE40) and 2 (BHLHE41) are involved in various fields such as circadian rhythms, immune responses, cell proliferation, hypoxia reaction as well as malignant tumors. Previous findings showed that DEC served as apoptosis regulators of various cancer cell lines. However, little is known regarding the expression of DEC1 and DEC2 in prostate cancer cells. The present study aimed to examine the roles of DEC1 and DEC2 in human prostate cancer DU145 and PC-3 cells that were treated with paclitaxel. The expression of DEC1 and DEC2 was decreased in DU145 cells but was increased in PC-3 cells when treated with paclitaxel. DU145 cells were more sensitive to paclitaxel than PC-3 cells since the amount of cleaved poly(ADP-ribose) polymerase (PARP) reached its peak at 50 μM of paclitaxel in DU145 cells but at 100 μM in PC-3 cells. In addition, the amount of cleaved PARP was decreased by DEC1 siRNA, while it was increased by DEC2 siRNA in the presence of paclitaxel. Although DEC2 overexpression slightly inhibited cleaved PARP in the two cell lines, the effects of DEC1 overexpression on apoptosis remain to be determined. In conclusion, DEC1, at least partly, exerted a pro-apoptotic effect, whereas DEC2 exerted an anti-apoptotic effect in paclitaxel-induced apoptosis of human prostate cancer cells.

Single cell RNA-sequencing identified Dec2 as a suppressive factor for spermatogonial differentiation by inhibiting Sohlh1 expression

“…Both DEC1 and DEC2 were later found to repress CLCOK/BMAL1-induced transactivation of the mouse Per1 promoter through direct protein-protein interaction with BMAL1 and/or competition for E-box elements 34 . More recently, the involvement of DEC2 in chondrocyte differentiation from mesenchymal stem cells 38–40 as well as cancer cell progression 56–58 has also been demonstrated. Strikingly, a recent scRNA-seq study also identified Dec2 as one of the DEGs preferentially expressed in mouse spermatogonia 12 , while its role in germ cells has not been investigated.…”

Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway

“…A number of studies have indicated a role for BHLHE41 in tumor development, though in different settings, different effects have been observed. Thus, BHLHE41 has been shown to promote oncogenesis in renal and prostate cancer [ 25 , 34 ]. In contrast, in breast, gastric and pancreatic cancer cells, anti-tumorigenic effects have been observed [ 35 – 37 ].…”

<p>BHLHE41 promotes U87 and U251 cell proliferation via ERK/cyclinD1 signaling pathway</p>

“…Initial studies on them have focused on embryonic development and tissue differentiation 3. Recent studies have shown that the deregulation of their expression is associated with tumor progression 5 , 7 , 9 , 10 , 12 , 13. Unlike BHLHE40, which is broadly expressed in many tissues, BHLHE41 showed a more restricted pattern of mRNA expression.…”