Research Paper Volume 12, Issue 17 pp 17122—17136
Long non-coding RNA SNHG12 promotes immune escape of ovarian cancer cells through their crosstalk with M2 macrophages
- 1 Department of Obstetrics and Gynecology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, P. R. China
- 2 Equal contribution
Received: March 28, 2020 Accepted: June 18, 2020 Published: September 14, 2020
https://doi.org/10.18632/aging.103653How to Cite
Abstract
Accumulating evidence shows that the tumor microenvironment contributes to this phenomenon and that long non-coding RNAs (lncRNAs) are also involved in this process. In this study, we identified a new lncRNA small nucleolar RNA host gene 12 (SNHG12) and investigated its role in tumor immune escape. We analyzed the expression levels of interlukin (IL)-6R and programmed death-ligand 1 (PD-L1) in 51 ovarian cancer and 20 normal specimens by immunohistochemistry. The correlation between SNHG12 and IL-6R in clinical ovarian cancer samples was identified by RT-qPCR. We then performed SNHG12 gain- and loss-function experiments in order to investigate its role in the regulation of immune escape and the crosstalk between miR-21 and IL-6. T cell proliferation was assessed by flow cytometry. In vivo pro-immune escape activity of SNHG12 was assessed by tumor-xenograft mouse model. IL-6R and PD-L1 were found to be overexpressed in clinical ovarian cancer specimens. Meanwhile, SNHG12 and IL-6R expressions were positively correlated in clinical ovarian cancer samples. SNHG12 facilitated ovarian immune escape by promoting IL-6/miR-21 crosstalk between ovarian cancer cells and M2 macrophages. Notably, SNHG12 promoted IL-6R transcription by recruiting NF-κB1 to the IL-6R promoter. Our study reveals that SNHG12 facilitates ovarian cancer immune escape by upregulating IL-6R.