miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1

Wei Jiang; Tao Li; Jingjing Wang; Ruonan Jiao; Xiao Shi; Xiaodan Huang; Guozhong Ji

doi:10.2147/OTT.S226465

miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1

Onco Targets Ther. 2019 Nov 27:12:10275-10285. doi: 10.2147/OTT.S226465. eCollection 2019.

Authors

Wei Jiang^#^{1

2}, Tao Li^#^{1

2}, Jingjing Wang^{1

2}, Ruonan Jiao^{1

2}, Xiao Shi^{1

2}, Xiaodan Huang^{1

2}, Guozhong Ji^{1

2}

Affiliations

¹ Department of Gastroenterology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People's Republic of China.
² Jiangsu Key Laboratory of Cancer Biomarkers, Prevention And Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, People's Republic of China.

^# Contributed equally.

Abstract

Background: A variety of miRNAs have been recently reported to be abnormally expressed in colorectal cancer (CRC). A growing number of studies have demonstrated that aberrantly expressed miRNAs are closely related to the development and progression of CRC. It has been found that miR-140-3p plays a vital role in several cancers. However, its expression, roles and mechanisms in CRC are remain unknown.

Materials and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine miR-140-3p expression in CRC tissues and cell lines. CCK8, migration, invasion and flow cytometric assays were used to determine the influence of miR-140-3p upregulation on cell proliferation, migration, invasion and apoptosis of CRC cells. Luciferase reporter assays and Western blots were utilized to identify the target genes of miR-140-3p. In addition, the potential mechanism of miR-140-3p action in CRC cells was elucidated.

Results: In our study, miR-140-3p expression was significantly decreased in CRC tissues and cell lines. Overexpression of miR-140-3p attenuated proliferation, migration, and invasion and induced the apoptosis of CRC cells. Bioinformatics analyse and luciferase reporter analysis identified PD-L1 as a putative target gene of miR-140-3p. PD-L1 was overexpressed in CRC tissues and inversely correlated with miR-140-3p expression. Suppression of PD-L1 expression in CRC cells generated biological behaviours in CRC cells that were similar to those observed after treated with miR-140-3p mimics. Restoration of PD-L1 expression partially attenuated the inhibitory effect of miR-140-3p on CRC cells. Western blot were used to verify the effect of PD-L1 expression on PI3K/AKT pathway. In addition, overexpression of miR-140-3p could inhibit CRC tumor growth in vivo.

Conclusion: In general, these data demonstrate that miR-140-3p acts as a tumour suppressor in CRC by directly targeting PD-L1 and inactivating PI3K/AKT pathway, suggesting that miR-140-3p might be a novel target for CRC diagnosis and treatment.

Keywords: PD-L1; apoptosis; colorectal cancer; microRNA-140-3p.