Long non-coding RNA SNHG12 promotes immune escape of ovarian cancer cells through their crosstalk with M2 macrophages

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.

PD-L1-Mediated Immunosuppression in Oral Squamous Cell Carcinoma: Relationship With Macrophage Infiltration and Epithelial to Mesenchymal Transition Markers

“…Classically, in response to microenvironmental stimuli, TAMs polarize to M1like phenotype exhibiting proinflammatory and tumor-inhibiting phenotypic effects, while certain cytokines convert TAMs into an M2-like phenotype with anti-inflammatory but tumor-promoting functions (38,39). Previous studies have shown that M2 macrophages elevated PD-L1 expression in cancer cells and at the same time facilitating immune escape (40,41). As for M1 macrophages, the PD-L1 expressed on the surface was also reported to result in immune escape of cancer cells, resulting in bidirectional effects of both anti-tumoral and pro-tumoral activities (42): On one hand, M1-like phenotype had the unique ability to promote the activation and recruitment of various immune effectors, performing surveillance tasks (43), and their infiltration indicated good prognosis in some cancers (44).…”

Screening and Identification of an Immune-Associated lncRNA Prognostic Signature in Ovarian Carcinoma: Evidence from Bioinformatic Analysis

“…Two lncRNAs AC104699.1.1 and RP11-284 N8.3.1 have been reported to exert protective effects throughout the progression of ovarian carcinoma and were related to the antitumor processes and activation of the immune system in the microenvironment [ 17 ]. A recent study showed that lncRNA SNHG12 facilitates immune escape of ovarian carcinoma cells by their crosstalk with M2 macrophages [ 18 ]. Therefore, it is reasonable to suggest that immune-associated lncRNAs may be the potential biomarkers for ovarian carcinoma patients and may serve as possible therapeutic targets.…”

SNHG12 Regulated by KMT2B Participates in the Pathogenesis of Renal Cell Carcinoma via E2F1/CEP55

“…SNHG12 exerts a carcinogenic effect in a variety of cancers [12][13][14][15][16][17][18][19][20][30][31][32]. In clear cell RCC, SNHG12, as a competitive endogenous RNA, competes with miR-30a-5p to bind downstream oncogenes RUNX2, IGF-1R and WNT2 to promote tumor cell invasiveness [33].…”