title: The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.
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.
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Gynaecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shuijing
authors.initials: S
authors.lastname: Yi
authors.affiliation: Department of Breast Oncology Plastic and Head and Neck, The Affiliated Cancer Hospital of Xiangya Medical School, Hunan, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Anliu
authors.initials: A
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China.
authors.forename: Shourong
authors.initials: S
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D060890:B7-H1 Antigen / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D016016:Proportional Hazards Models
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C546110:MIRN138 microRNA, human; D035683:MicroRNAs
keywords: PD-L1; biomarker; colorectal cancer; miR-138-5p; tumor suppressor