Abstract
Long non-coding RNAs (lncRNAs), as promising novel biomarkers for cancer treatment and prognosis, can function as tumor suppressors and oncogenes in the occurrence and development of many types of cancer, including gastric cancer (GC). However, little is known about the complex regulatory system of lncRNAs in GC. In this study, we systematically analyzed lncRNA and miRNA transcriptomic profiles of GC based on bioinformatics methods and experimental validation. An lncRNA-miRNA interaction network related to GC was constructed, and the nine crucial lncRNAs were identified. These 9 lncRNAs were found to be associated with the prognosis of GC patients by Cox proportional hazards regression analysis. Among them, the expression of lncRNA SNHG14 can affect the survival of GC patients as a potential prognostic marker. Moreover, it was shown that SNHG14 was involved in immune-related pathways and significantly correlated with immune cell infiltration in GC. Meanwhile, we found that SNHG14 affected immune function in many cancers, such as breast cancer and esophageal carcinoma. Such information revealed that SNHG14 may serve as a potential target for cancer immunotherapy. As well, our study could provide practical and theoretical guiding significance for clinical application of non-coding RNAs.
Similar content being viewed by others
Data Availability
All data analyzed during the present study are publicly available at TCGA data portal (https://portal.gdc.cancer.gov/).
References
Ahadi A (2021) A systematic review of microRNAs as potential biomarkers for diagnosis and prognosis of gastric cancer, Immunogenetics
Ashwini J et al (2012) Debora, miRcode: a map of putative microRNA target sites in the long non-coding transcriptome, Bioinformatics
Damian S, Gable AL, Nastou KC et al (2020) The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res D1
Di W, Weinan X, Xin L et al (2019) Long noncoding RNA SNHG14 facilitates colorectal cancer metastasis through targeting EZH2-regulated EPHA7. Cell Death Dis 10:514
Far BF, Vakili K, Fathi M et al (2023) The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: a review. Life Sci 316:121340
Gao Y, Wang J, Ren J et al (2020) Long noncoding RNAs in gastric cancer: from molecular dissection to clinical application. World J Gastroenterol 26:3401–3412
Gao Z, Han H, Zhao Y et al (2021) A tumor microenvironment-related mRNA-ncRNA signature for prediction early relapse and chemotherapeutic sensitivity in early-stage lung adenocarcinoma. J Cancer Res Clin Oncol 147:3195–3209
Goodall G, Wickramasinghe V (2021) RNA in cancer, Nature reviews. Cancer 21:22–36
He C, Liu Y, Li J et al (2022) LncRNA RPSAP52 promotes cell proliferation and inhibits cell apoptosis via modulating miR-665/STAT3 in gastric cancer. Bioengineered 13:8699–8711
Hosseini SA, Haddadi MH, Fathizadeh H et al (2023) Long non-coding RNAs and gastric cancer: an update of potential biomarkers and therapeutic applications. Biomed Pharmacotherapy = Biomedecine Pharmacotherapie 163:114407
Huang HY, Lin Y, Li J et al (2019) miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database. Nuclc Acids Res
Huang D, Zhang K, Zheng W et al (2021) Long noncoding RNA SGO1-AS1 inactivates TGFβ signaling by facilitating TGFB1/2 mRNA decay and inhibits gastric carcinoma metastasis. J Experimental Clin cancer Research: CR 40:342
Ishaque N, Abba M, Hauser C et al (2018) Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer. Nat Commun 9:4782
Jager KJ, van Dijk PC, Zoccali C et al (2008) The analysis of survival data: the Kaplan-Meier method. Kidney Int 74:560–565
Jia Y, Yan Q, Zheng Y et al (2022) Long non-coding RNA NEAT1 mediated RPRD1B stability facilitates fatty acid metabolism and lymph node metastasis via c-Jun/c-Fos/SREBP1 axis in gastric cancer. J Experimental Clin cancer Research: CR 41:287
Kanda M, Tanaka H, Shimizu D et al (2018) SYT7 acts as a driver of hepatic metastasis formation of gastric cancer cells. Oncogene 37:5355–5366
Kaufmann SHE (2019) Immunology’s coming of Age. Front Immunol 10:684
Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303
Li H, Long C, Xiang J et al (2020a) Dppa2/4 as a trigger of signaling pathways to promote zygote genome activation by binding to CG-rich region. Brief Bioinform
Li Y, Jiang T, Zhou W et al (2020b) Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers. Nat Commun 11:1000
Li J, Zhang C, Shi Y et al (2021a) Identification of KEY lncRNAs and mRNAs Associated with oral squamous cell carcinoma progression. Curr Bioinform 16:207–215
Li C, Tang Z, Zhang W et al (2021b) GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA. Nucleic Acids Res 49:W242–W246
Li X, Du Y, Wang Y (2021c) The value of LncRNA SNHG5 as a marker for the diagnosis and prognosis of gastric cancer. Am J Translational Res 13:5420–5427
Li D, Xu M, Wang Z et al (2022) The EMT-induced lncRNA NR2F1-AS1 positively modulates NR2F1 expression and drives gastric cancer via miR-29a-3p/VAMP7 axis. Cell Death Dis 13:84
Liang P, Yang W, Chen X et al (2020) Machine learning of single-cell transcriptome highly identifies mRNA signature by comparing F-Score selection with DGE analysis. Mol Therapy - Nucleic Acids 20:155–163
Liang P, Zheng L, Long C et al (2021) HelPredictor models single-cell transcriptome to predict human embryo lineage allocation, 22
Liao Z, Zhang H, Su C et al (2021) Long noncoding RNA SNHG14 promotes hepatocellular carcinoma progression by regulating miR-876-5p/SSR2 axis. J Experimental Clin cancer Research: CR 40:36
Lin Z, Song J, Gao Y et al (2022) Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer. Redox Biol 52:102312
Liu G, Li H, Ji W et al (2021) Construction of a ceRNA network in glioma and analysis of its clinical significance. BMC Genomics 22:722
Love MI, Huber W, Anders S (2014) Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550
Ma Z, Shuai Y, Gao X et al (2020) BTEB2-Activated lncRNA TSPEAR-AS2 drives GC progression through suppressing GJA1 expression and upregulating CLDN4 expression, Molecular therapy. Nucleic Acids 22:1129–1141
Piao H, Liu Y, Kang Y et al (2021) Hypoxia associated lncRNA HYPAL promotes proliferation of gastric cancer as ceRNA by sponging mir-431-5p to upregulate CDK14, gastric cancer: official. J Int Gastric Cancer Association Japanese Gastric Cancer Association
Rugolo F, Bazan N, Calandria J et al (2021) The expression of ELOVL4, repressed by MYCN, defines neuroblastoma patients with good outcome, Oncogene
Slack FJ, Chinnaiyan AM (2019) The role of non-coding RNAs in Oncology. Cell 179:1033–1055
Tang W, Wan S, Yang Z et al (2018) Tumor origin detection with tissue-specific miRNA and DNA methylation markers. Bioinf (Oxford England) 34:398–406
Tang Q, Shi X, Xu Y et al (2023) Identification and Validation of the Diagnostic Markers for Inflammatory Bowel Disease by Bioinformatics Analysis and Machine Learning, Biochemical genetics
Tian Y, Li L, Lin G et al (2021) lncRNA SNHG14 promotes oncogenesis and immune evasion in diffuse large-B-cell lymphoma by sequestering miR-152-3p. Leuk Lymphoma 62:1574–1584
Wang M, Yu F, Chen X et al (2020) The underlying mechanisms of noncoding RNAs in the Chemoresistance of Hepatocellular Carcinoma, Molecular therapy. Nucleic Acids 21:13–27
Wang H, Liang P, Zheng L et al (2021) eHSCPr discriminating the cell identity involved in endothelial to hematopoietic transition, Bioinformatics
Wang C, Zhao D, Shu X et al (2022) Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis. J Cancer Res Clin Oncol 148:121–135
Wei Z, Chen L, Meng L et al (2020) LncRNA HOTAIR promotes the growth and metastasis of gastric cancer by sponging mir-1277-5p and upregulating COL5A1. Gastric Cancer 23
Wu Q, Zhang B, Wang Z et al (2019) Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gastric cancer. Pathol Res Pract 215:1038–1048
Xiao T, Jie Z (2019) MiR-21 promotes the Invasion and Metastasis of Gastric Cancer cells by activating epithelial-mesenchymal transition, European surgical research. Europaische Chirurgische Forschung Recherches Chirurgicales Europeennes 60:208–218
Xie S, Chang Y, Jin H et al (2020) Non-coding RNAs in gastric cancer. Cancer Lett
Xu MD, Wang Y, Weng W et al (2017) A positive Feedback Loop of lncRNA-PVT1 and FOXM1 facilitates gastric Cancer Growth and Invasion. Clin cancer Research: Official J Am Association Cancer Res 23:2071–2080
Yang Q, Wu J, Zhao J et al (2020) The expression profiles of lncRNAs and their Regulatory Network during Smek1/2 knockout mouse neural stem cells differentiation. Curr Bioinform 15:77–88
Yang Z, Li Q, Zheng X et al (2021) Long noncoding RNA small nucleolar host gene: a potential therapeutic target in Urological Cancers. Front Oncol 11:638721
Yang H, Hu Y, Weng M et al (2022) Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. J Adv Res 37:91–106
Zhang W, Duan W, Mo Z et al (2020) Upregulation of SNHG14 suppresses cell proliferation and metastasis of colorectal cancer by targeting miR-92b-3p. J Cell Biochem 121:1998–2008
Zhang Y, Dong X, Guo X et al (2023) LncRNA-BC069792 suppresses tumor progression by targeting KCNQ4 in breast cancer. Mol Cancer 22:41
Zhao L, Guo H, Zhou B et al (2016) Long non-coding RNA SNHG5 suppresses gastric cancer progression by trapping MTA2 in the cytosol. Oncogene 35:5770–5780
Zhao L, Han T, Li Y et al (2017) The lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and migration by targeting KLF4, FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 31:893–903
Zhao L, Liu Y, Zhang J et al (2019) LncRNA SNHG14/miR-5590-3p/ZEB1 positive feedback loop promoted diffuse large B cell lymphoma progression and immune evasion through regulating PD-1/PD-L1 checkpoint. Cell Death Dis 10:731
Zhao C, Xu H, Liu C (2023) Identification of Novel Prognostic Long Non-coding RNAs in Lung Adenocarcinoma Using WGCNA Analysis, Biochemical genetics
Zhuo W, Liu Y, Li S et al (2019) Long noncoding RNA GMAN, Up-regulated in gastric Cancer tissues, is Associated with metastasis in patients and promotes translation of ephrin A1 by competitively binding GMAN-AS. Gastroenterology 156:676–691e611
Acknowledgements
This work was financially supported by Natural Science Foundation of Inner Mongolia (No. 2022QN06007); the National Natural Science Foundation of China (No. 81960449, 62171241 and 62061034); the Science Research Foundation of Inner Mongolia People’s Hospital (No. 2021YN18); the Science and Technology Planning Project for Health of Inner Mongolia (No. 202202024); and the Talent Training Plan for the Key Laboratory of Inner Mongolia Science and Technology Department.
Author information
Authors and Affiliations
Contributions
W.J. and J.J. contributed to the design, bioinformatics analysis, drafting and writing of the manuscript. Y.S. and H.L. participated in data analysis. J.L. devoted the work of negotiation and revising the manuscript. H.Z. and Z.W. performed samples collection and biological experiment. L.Y. and Y.Z. provided full guidance of the study. All authors have read and approved the final manuscript for submission.
Corresponding authors
Ethics declarations
Ethics Approval and Consent to Participate
The tissue samples used in this study have been approved by the Medical Ethics Committee of Inner Mongolia People’s Hospital. All of the patients signed the informed consent for beforehand.
Consent for Publication
Not applicable.
Competing Interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Jin, W., Jia, J., Si, Y. et al. Identification of Key lncRNAs Associated with Immune Infiltration and Prognosis in Gastric Cancer. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10801-w
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10528-024-10801-w