Identification and Validation of LncRNA-SNHG17 in Lung Adenocarcinoma: A Novel Prognostic and Diagnostic Indicator

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jun 20

PMID 35719962

Authors

Xinyan Li

Yixiao Yuan

Mintu Pal

Xiulin Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer has the highest death rate among cancers globally. Accumulating evidence has indicated that cancer-related inflammation plays an important role in the initiation and progression of lung cancer. However, the prognosis, immunological role, and associated regulation axis of inflammatory response-related gene (IRRGs) in non-small-cell lung cancer (NSCLC) remains unclear.

Methods: In this study, we perform comprehensive bioinformatics analysis and constructed a prognostic inflammatory response-related gene (IRRGs) and related competing endogenous RNA (ceRNA) network. We also utilized the Pearson's correlation analysis to determine the correlation between IRRGs expression and tumor mutational burden (TMB), microsatellite instability (MSI), tumor-immune infiltration, and the drug sensitivity in NSCLC. Growth curve and Transwell assay used to verify the function of SNHG17 on NSCLC progression.

Results: First, we found that IRRGs were significantly upregulated in lung cancer, and its high expression was correlated with poor prognosis; high expression of IRRGs was significantly correlated with the tumor stage and poor prognosis in lung cancer patients. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that these IRRGs are mainly involved in the inflammatory and immune response-related signaling pathway in the progression of NSCLC. We utilized 10 prognostic-related genes to construct a prognostic IRRGs model that could predict the overall survival of lung adenocarcinoma (LUAD) patients possessing high specificity and accuracy. Our evidence demonstrated that IRRGs expression was significantly correlated with the TMB, MSI, immune-cell infiltration, and diverse cancer-related drug sensitivity. Finally, we identified the upstream regulatory axis of IRRGs in NSCLC, namely, lncRNA MIR503HG/SNHG17/miR-330-3p/regulatory axis. Finally, knockdown of SNHG17 expression inhibited lung adenocarcinoma (LUAD) cell proliferation and migration. Our findings confirmed that SNHG17 is a novel oncogenic lncRNA and may be a biomarker for the prognosis and diagnosis of LUAD.

Conclusion: DNA hypomethylation/lncRNA MIR503HG/SNHG17/microRNA-330-3p/regulatory axis may be a valuable biomarker for prognosis and is significantly correlated with immune cell infiltration in lung cancer.

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References

Liu L, Zhou X, Zhang J, Wang G, He J, Chen Y . LncRNA HULC promotes non-small cell lung cancer cell proliferation and inhibits the apoptosis by up-regulating sphingosine kinase 1 (SPHK1) and its downstream PI3K/Akt pathway. Eur Rev Med Pharmacol Sci. 2018; 22(24):8722-8730. DOI: 10.26355/eurrev_201812_16637. View

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

Yuan M, Zhu H, Xu J, Zheng Y, Cao X, Liu Q . Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils. J Immunol Res. 2016; 2016:6530410. PMC: 4942661. DOI: 10.1155/2016/6530410. View

Saab S, Zalzale H, Rahal Z, Khalifeh Y, Sinjab A, Kadara H . Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment. Front Immunol. 2020; 11:159. PMC: 7026250. DOI: 10.3389/fimmu.2020.00159. View

Zhang Y, Lai H, Chen P, Li D, Khan I, Hsiao W . Clinical significance of LSECtin and its association with PVR in non-small-cell lung cancer patients. Ann Transl Med. 2020; 8(21):1393. PMC: 7723651. DOI: 10.21037/atm-20-3665. View

Li J, Liu S, Zhou H, Qu L, Yang J . starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 2013; 42(Database issue):D92-7. PMC: 3964941. DOI: 10.1093/nar/gkt1248. View

Sticht C, de la Torre C, Parveen A, Gretz N . miRWalk: An online resource for prediction of microRNA binding sites. PLoS One. 2018; 13(10):e0206239. PMC: 6193719. DOI: 10.1371/journal.pone.0206239. View

Chen Y, Wang X . miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 2019; 48(D1):D127-D131. PMC: 6943051. DOI: 10.1093/nar/gkz757. View

10.

Dao R, Wudu M, Hui L, Jiang J, Xu Y, Ren H . Knockdown of lncRNA MIR503HG suppresses proliferation and promotes apoptosis of non-small cell lung cancer cells by regulating miR-489-3p and miR-625-5p. Pathol Res Pract. 2020; 216(3):152823. DOI: 10.1016/j.prp.2020.152823. View

11.

Zhang T, Guo J, Gu J, Wang Z, Wang G, Li H . Identifying the key genes and microRNAs in colorectal cancer liver metastasis by bioinformatics analysis and in vitro experiments. Oncol Rep. 2018; 41(1):279-291. PMC: 6278419. DOI: 10.3892/or.2018.6840. View

12.

Zhou J, Kwak K, Wu Z, Yang D, Li J, Chang M . PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway. Cell Physiol Biochem. 2018; 47(5):1909-1924. DOI: 10.1159/000491071. View

13.

Diakos C, Charles K, McMillan D, Clarke S . Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014; 15(11):e493-503. DOI: 10.1016/S1470-2045(14)70263-3. View

14.

Neagu M, Constantin C, Caruntu C, Dumitru C, Surcel M, Zurac S . Inflammation: A key process in skin tumorigenesis. Oncol Lett. 2019; 17(5):4068-4084. PMC: 6444305. DOI: 10.3892/ol.2018.9735. View

15.

Xu Y, Liu H, Liu S, Wang Y, Xie J, Stinchcombe T . Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer. Int J Cancer. 2018; 143(10):2400-2408. PMC: 6205899. DOI: 10.1002/ijc.31660. View

16.

Ma Y, Xing X, Kong R, Cheng C, Li S, Yang X . SphK1 promotes development of non‑small cell lung cancer through activation of STAT3. Int J Mol Med. 2020; 47(1):374-386. DOI: 10.3892/ijmm.2020.4796. View

17.

Qian S, Golubnitschaja O, Zhan X . Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles. EPMA J. 2019; 10(4):365-381. PMC: 6882964. DOI: 10.1007/s13167-019-00194-x. View

18.

Cao Z, Pan X, Yang Y, Huang Y, Shen H . The lncLocator: a subcellular localization predictor for long non-coding RNAs based on a stacked ensemble classifier. Bioinformatics. 2018; 34(13):2185-2194. DOI: 10.1093/bioinformatics/bty085. View

19.

Jiang X, Yuan Y, Tang L, Wang J, Liu Q, Zou X . Comprehensive Pan-Cancer Analysis of the Prognostic and Immunological Roles of the METTL3/lncRNA-SNHG1/miRNA-140-3p/UBE2C Axis. Front Cell Dev Biol. 2021; 9:765772. PMC: 8631498. DOI: 10.3389/fcell.2021.765772. View

20.

Wang G, Cheng X, Li X, Liu Y, Wang X, Shi X . Tobacco smoke induces production of chemokine CCL20 to promote lung cancer. Cancer Lett. 2015; 363(1):60-70. DOI: 10.1016/j.canlet.2015.04.005. View