The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer

// Lian Zhao 1, 2 , Haibo Yu 3 , Shuijing Yi 4 , Xiaowei Peng 5 , Peng Su 1, 2 , Zhiming Xiao 1 , Rui Liu 1 , Anliu Tang 1, 2 , Xiayu Li 1, 2 , Fen Liu 1, 2 , Shourong Shen 1, 2 1 Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China 3 Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China 4 Department of Gynaecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China 5 Department of Breast Oncology Plastic and Head and Neck, The Affiliated Cancer Hospital of Xiangya Medical School, Hunan, China Correspondence to: Haibo Yu, e-mail: yuhaibo616@163.com Keywords: miR-138-5p, PD-L1, tumor suppressor, colorectal cancer, biomarker Received: August 21, 2015 Accepted: May 13, 2016 Published: May 27, 2016 ABSTRACT microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3′ untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo . PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.