BHLHE41 Enhances Gemcitabine Sensitivity of Pancreatic Cancer Cells Through IGFBP4 Suppression.

[BACKGROUND/AIM] Pancreatic cancer (PC) has a poor prognosis and limited treatment options. The development of resistance to anticancer agents poses a significant challenge in the treatment of PC. Our previous study indicated that basic helix-loop-helix family member e41 (BHLHE41) is associated with the prognosis of lung cancer. Additionally, BHLHE41 affects the prognosis and response to anticancer drugs in several cancers. However, the functional role of BHLHE41 in cancer remains unclear. In PC, its expression has been reported to influence tumor malignancy; however, its impact on chemosensitivity has not yet been elucidated. Therefore, this study aimed to investigate the effects of BHLHE41 on PC chemosensitivity.

[MATERIALS AND METHODS] Genetic modification and MTT assays were performed to evaluate the effect of BHLHE41 on anticancer agents. RNA sequencing (RNA-seq) was conducted to analyze the downstream pathways of BHLHE41. Furthermore, anticancer agent sensitivity tests were performed for the candidate genes identified through RNA-seq.

[RESULTS] BHLHE41 enhanced the sensitivity of PC cells to gemcitabine (GEM) while suppressing the expression of insulin-like growth factor binding protein 4 (IGFBP4). Additionally, IGFBP4 affected sensitivity to GEM independently of BHLHE41, suggesting that IGFBP4 contributes to resistance to this agent in PC cells.

[CONCLUSION] These findings provide novel insights that may help identify potential targets for patients with PC undergoing chemotherapy and open new avenues for research and therapeutic strategies.