Enhancement of Sensitivity to Chemo/Radiation Therapy by Using miR-15b against DCLK1 in Colorectal Cancer

Abstract

Summary: Chemo-/radiotherapy resistance is the main cause accounting for most treatment failure in colorectal cancer (CRC). Tumor-initiating cells (TICs) are the culprit leading to CRC chemo-/radiotherapy resistance. The underlying regulation mechanism of TICs in CRC remains unclear. Here we discovered that miR-15b expression positively correlated with therapeutic outcome in CRC. Expression of miR-15b in pretreatment biopsy tissue samples predicted tumor regression grade (TRG) in rectal cancer patients after receiving neoadjuvant radiotherapy (nRT). Expression of miR-15b in post-nRT tissue samples was associated with therapeutic outcome. DCLK1 was identified as the direct target gene for miR-15b and its suppression was associated with self-renewal and tumorigenic properties of DCLK1+ TICs. We identified B lymphoma Mo-MLV insertion region l homolog (BMI1) as a downstream target regulated by miR-15b/DCLK1 signaling. Thus, miR-15b may serve as a valuable marker for prognosis and therapeutic outcome prediction. DCLK1 could be a potential therapeutic target to overcome chemo-/radioresistance in CRC. : Gu et al. identified that DCLK1 regulates the behavior of CRC TIC and is associated with chemo-/radiotherapy resistance. Expression of DCLK1 reversely correlated with prognosis and chemo-/radiotherapeutic outcome in CRC. miR-15b is able to sensitize the tumor cells to chemo-/radiotherapy by targeting DCLK1. miR-15b is a favorite factor for the prognosis and chemo-/radiotherapeutic outcome in clinical samples. Keywords: colorectal cancer, chemo-/radiotherapy, miR-15b, DCLK1