LncRNA PROX1-AS1 Facilitates Gastric Cancer Progression via miR-877-5p/PD-L1 Axis

TianWei Guo; Wei Wang; YueXia Ji; Min Zhang; GuoYing Xu; Sen Lin

doi:10.2147/CMAR.S275352

LncRNA PROX1-AS1 Facilitates Gastric Cancer Progression via miR-877-5p/PD-L1 Axis

Cancer Manag Res. 2021 Mar 19:13:2669-2680. doi: 10.2147/CMAR.S275352. eCollection 2021.

Authors

TianWei Guo^#¹, Wei Wang^#², YueXia Ji¹, Min Zhang³, GuoYing Xu⁴, Sen Lin⁵

Affiliations

¹ Department of Pathology, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, Jiangsu, People's Republic of China.
² Department of Pathology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, People's Republic of China.
³ Department of Pathology, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, People's Republic of China.
⁴ School of Medical Technology, Jiangsu College of Nursing, Huai'an, Jiangsu, People's Republic of China.
⁵ The Affiliated Huai'an Hospital of Xuzhou Medical University and the Second People's Hospital of Huai'an, Huai'an, Jiangsu, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: Growing evidences imply that multiple long non-coding RNAs (lncRNAs) play a significant role in the treatment of cancer. Therefore, it is of great significance to discover new biomarkers or therapeutic targets of gastric cancer (GC). However, the potential molecular mechanism of lncPROX1-AS1 in GC remains unknown. The objective of current study is to investigate the effect of PROX1-AS1 in GC.

Methods: Thus, we detect that PROX1-AS1 is over-expressed in tissues and cell lines of GC using qRT-PCR analysis. CCK-8, colony formation, flow cytometry, wounding healing and transwell analyses were performed to explore the effect of PROX1-AS1 on GC malignant behaviors.

Results: It is further disclosed that silencing of PROX1-AS1 represses cell proliferation, migration, and invasion, whereas promotes cell apoptosis in GC. Bioinformatics analysis suggests that miR-877-5p is negatively regulated by PROX1-AS1 and ectopic of miR-877-5p alleviates the malignant behaviors of GC. Subsequently, miR-877-5p suppresses the activity of PD-L1-3' UTR. At last, rescue assays demonstrated that the GC progression is suppressed by sh-PROX1-AS1 and facilitated on account of miR-877-5p inhibitors and then is retrieved by sh-PD-L1.

Discussion: Our findings reveal that PROX1-AS1 exerts its role via miR-877-5p/PD-L1 axis in the GC progression, suggesting that PROX1-AS1 may represent a new therapeutic target for the diagnosis and treatment of GC patients.

Keywords: PD-L1; PROX1-AS1; apoptosis; gastric cancer; miR-877-5p; proliferation.

Grants and funding

Changshu Municipal Health and Family Planning Commission Science and Technology Plan Youth Project (No. cswsq201809) and Suzhou science and technology development plan project (Livelihood Science and technology-Basic Research on medical and health application) (No: SYSD2018020).