TY  - EJOU
AU  - Zhang, Feng 
AU  - Sun, Hong 
AU  - Zhang, Sai 
AU  - Yang, Xin 
AU  - Zhang, Guogang 
AU  - Su, Tao 

TI  - Overexpression of PER3 Inhibits Self-Renewal Capability and  Chemoresistance of Colorectal Cancer Stem-Like Cells  via Inhibition of Notch and β-Catenin Signaling
T2  - Oncology Research

PY  - 2017
VL  - 25
IS  - 5
SN  - 1555-3906

AB  - PER3, a circadian clock gene, plays an important role in colorectal cancer, but its action and underlying mechanism in colorectal cancer stem-like cells (CSCs) remain unclear. In this study, the colorectal CSCs were 
enriched in colorectal HCT-116 sphere-forming cells, expressing lower levels of stem cell markers CD133, 
CD44, LGR5, and SOX2 compared with HCT-116 cells. A drug-resistant strain from HCT-116 was established. 
Western blot and qRT-PCR analysis showed that PER3 was downregulated in colorectal CSCs and drug-resistant 
HCT-116. Overexpression of PER3 could strengthen 5-FU-induced inhibitory effects on colorectal CSCs, but 
knockdown of PER3 decreased its inhibition of colorectal CSCs. In addition, overexpression of PER3 in colorectal CSCs resulted in reduced colony formation efficiency in a soft agar medium and self-renewal efficiency. Inversely, knockdown of PER3 enhanced self-renewal of colorectal CSCs. Overexpression of PER3 
decreased stemness markers and Notch1, Jagged1, β-catenin, c-Myc, and LGR5 in colorectal CSCs. When 
Notch or β-catenin signaling was inhibited, the chemoresistance and self-renewal capability of colorectal CSCs 
were decreased. It was confirmed that PER3 can reduce chemoresistance and self-renewal capability of colorectal CSCs via inhibition of Notch and β-catenin signaling. Our results reveal that PER3 plays a critical role 
in maintaining the stemness of colorectal CSCs and may be a promising target for elimination of CSCs.
KW  - Colorectal cancer stem-like cells (CSCs); Circadian clock; PER3; Self-renewal;  Chemoresistance

DO  - 10.3727/096504016X14772331883976