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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-?B1 to the IL-6R promoter. Our study reveals that SNHG12 facilitates ovarian cancer immune escape by upregulating IL-6R.

SUBMITTER: Qian M

PROVIDER: S-EPMC7521506 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Qian Min M Ling Wanwen W Ruan Zhengyi Z

Aging 20200914 17

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 I ...[more]

PMID: 32927431

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Project description:Recently, increasing studies suggested that lncRNA SNHG12 was aberrantly expressed in kinds of cancers. However, definite prognostic value of SNHG12 remains unclear. We conducted this meta-analysis to evaluate the association between SNHG12 expression level and cancer prognosis. A literature retrieval was conducted by searching kinds of databases. The meta-analysis was performed by using Revman 5.2 and Stata 12.0 software. Besides, The Cancer Genome Atlas dataset was analyzed to validate the results in our meta-analysis via using Gene Expression Profiling Interactive Analysis. The pooled results showed that high SNHG12 expression significantly indicated worse overall survival and recurrence-free survival. Tumor type, sample size, survival analysis method, and cutoff value did not alter SNHG12 prognosis value according to stratified analysis results. Additionally, higher expression of SNHG12 suggested unfavorable clinicopathological outcomes including larger tumor size, lymph node metastasis, distant metastasis, and advanced clinical stage. Online cross-validation in TCGA dataset further indicated that cancer patients with upregulated SNHG12 expression had worse overall survival and disease-free survival. Therefore, elevated SNHG12 expression was associated with poor survival and unfavorable clinical outcomes in various cancers, and therefore might be a potential prognostic biomarker in human cancers. Abbreviations Akt: protein kinase B; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; ceRNA: competitive endogenous RNA; CNKI: China National Knowledge Infrastructure; CI: confidence interval; CCNE1: cyclin E1; COAD: colon adenocarcinoma; DM: distant metastasis; DFS: disease-free survival; EMT: epithelial-mesenchymal transition; FISH: fluorescence in situ hybridization; FIGO: the International Federation of Gynecology and Obstetrics; GEPIA: Gene Expression Profiling Interactive Analysis; HR: hazard ratio; HIFα: hypoxia-inducible factor 1 α; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LIHC: hepatocellular carcinoma; LNM: lymph node metastasis; mTOR: mechanistic target of rapamycin kinase; MMP-9: matrix metalloproteinase 9; MCL1: myeloid cell leukemia 1; MLK3: mixed-lineage protein kinase 3; N/A: not available; NOS: Newcastle-Ottawa Scale; OR: odd ratio; OS: overall survival; PSA: prostate-specific antigen; PI3K: phosphoinositide 3-kinase; qRT-PCR: quantitative real-time polymerase chain reaction; READ: rectum adenocarcinoma; RFS: recurrence-free survival; SARC: sarcoma; SNHG12: small nucleolar RNA host gene 12; STAT3: signal transducer and activator of transcription 3; SOX4: SRY-box transcription factor 4; SOX5: SRY-box transcription factor 5; STAD: stomach adenocarcinoma; TCGA: The Cancer Genome Atlas; TNM: tumor node metastasis; WWP1: WW domain-containing E3 ubiquitin protein ligase 1; WHO grade: World Health Organization grade; ZEB2: zinc finger E-box-binding homeobox 2.

Dataset Information

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

Publications

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

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