Oncotarget

Research Papers:

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

Lian Zhao, Haibo Yu _, Shuijing Yi, Xiaowei Peng, Peng Su, Zhiming Xiao, Rui Liu, Anliu Tang, Xiayu Li, Fen Liu and Shourong Shen

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Oncotarget. 2016; 7:45370-45384. https://doi.org/10.18632/oncotarget.9659

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Abstract

Lian Zhao1,2, Haibo Yu3, Shuijing Yi4, Xiaowei Peng5, Peng Su1,2, Zhiming Xiao1, Rui Liu1, Anliu Tang1,2, Xiayu Li1,2, Fen Liu1,2, Shourong Shen1,2

1Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

2Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, China

3Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

4Department of Gynaecology and Obstetrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

5Department 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.


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