Abstract | BACKGROUND: METHODS: Comprehensive bioinformatics analysis was performed to identify immunosuppressive lncRNAs involved with tumour invasion in NSCLC. The expression levels of PCAT1 were analysed by in situ hybridisation in 55 paired NSCLC tissues and adjacent normal tissues. Both loss- and gain-of-function assays were performed to examine the effects of PCAT1 and SOX2 on NSCLC cell behaviours in vivo and in vitro. Bioinformatic analyses, chromatin isolation by RNA purification (ChIRP) and dual- luciferase reporter assays were applied to validate the regulatory effects of PCAT1 on SOX2 expression. Chromatin immunoprecipitation, luciferase and rescue assays were utilised to identify the relationship between SOX2 and the cGAS/stimulator of interferon genes ( STING) signalling. RESULTS: PCAT1 was immunosuppressive and related with NSCLC invasion. Increased PCAT1 was negatively correlated with immune cell infiltration in NSCLC. PCAT1 knockdown restrained proliferation, increased apoptosis, and repressed cell metastasis in vivo and in vitro. PCAT1 activated SOX2 that accelerated tumorigenesis and immunosuppression. SOX2 promoted tumour growth through inhibiting cytotoxic T-cell immunity. Moreover, SOX2 restrained cGAS transcription and hampered downstream type I interferon (IFN)-induced immune responses. Inhibition of PCAT1/SOX2 in collaboration with radiation further inhibited tumour growth, and initiated the cGAS/ STING signalling pathway, which enhanced the immune responses of radiotherapy in NSCLC. CONCLUSIONS: PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/ STING signalling-mediated T-cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets.
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Authors | Yanping Gao, Nannan Zhang, Zihang Zeng, Qiuji Wu, Xueping Jiang, Shuying Li, Wenjie Sun, Jianguo Zhang, Yangyi Li, Jiali Li, Fajian He, Zhengrong Huang, Jinfang Zhang, Yan Gong, Conghua Xie |
Journal | Clinical and translational medicine
(Clin Transl Med)
Vol. 12
Issue 4
Pg. e792
(04 2022)
ISSN: 2001-1326 [Electronic] United States |
PMID | 35415876
(Publication Type: Journal Article)
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Copyright | © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. |
Chemical References |
- Membrane Proteins
- RNA, Long Noncoding
- SOX2 protein, human
- SOXB1 Transcription Factors
- STING1 protein, human
- long non-coding RNA PCAT1, human
- Nucleotidyltransferases
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Topics |
- Carcinogenesis
(genetics)
- Carcinoma, Non-Small-Cell Lung
(genetics, metabolism, pathology)
- Humans
- Lung Neoplasms
(genetics, metabolism, pathology)
- Male
- Membrane Proteins
(metabolism)
- Nucleotidyltransferases
(genetics, metabolism)
- RNA, Long Noncoding
(genetics, metabolism)
- SOXB1 Transcription Factors
(genetics)
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