Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation

Author(s): Yuan Yuan, Qian Li, Feifei Chen, Yujie Zhao, Jiyong Ma* and Surong Fang*

Volume 31, Issue 28, 2024

Published on: 27 November, 2023

Page: [4549 - 4561] Pages: 13

DOI: 10.2174/0109298673280925231122104717

Price: $65

Abstract

Aim: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD).

Background: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined.

Objective: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation.

Methods: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis.

Results: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects.

Conclusion: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.

« Previous Next »
[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Herbst, R.S.; Morgensztern, D.; Boshoff, C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689), 446-454.
[http://dx.doi.org/10.1038/nature25183] [PMID: 29364287]
[3]
Chen, D.; Wang, R.; Yu, C.; Cao, F.; Zhang, X.; Yan, F.; Chen, L.; Zhu, H.; Yu, Z.; Feng, J. FOX-A1 contributes to acquisition of chemoresistance in human lung adenocarcinoma via transactivation of SOX5. EBioMedicine, 2019, 44, 150-161.
[http://dx.doi.org/10.1016/j.ebiom.2019.05.046] [PMID: 31147293]
[4]
Xu, L.; Li, K.; Li, J.; Liu, L.; Xu, F.; Xu, Y.; Kong, Y.; Pu, X.; Wang, Q.; Wang, J.; Chen, B.; Wu, L. MiR-21/sonic hedgehog (SHH)/PI3K/AKT pathway is associated with NSCLC of primary EGFR-TKI resistance. Oncologie, 2022, 24(3), 579-590.
[http://dx.doi.org/10.32604/oncologie.2022.022121]
[5]
Song, Y.; Yan, S.; Fan, W.; Zhang, M.; Liu, W.; Lu, H.; Cao, M.; Hao, C.; Chen, L.; Tian, F.; Zhan, Y.; Cai, L.; Xing, Y. Identification and validation of the immune subtypes of lung adenocarcinoma: Implications for immunotherapy. Front. Cell Dev. Biol., 2020, 8, 550.
[http://dx.doi.org/10.3389/fcell.2020.00550] [PMID: 32719796]
[6]
Zhang, L.; Yu, D. Exosomes in cancer development, metastasis, and immunity. Biochim. Biophys. Acta Rev. Cancer, 2019, 1871(2), 455-468.
[http://dx.doi.org/10.1016/j.bbcan.2019.04.004] [PMID: 31047959]
[7]
Zhang, H.; Wang, X.; Yu, Y.; Yang, Z. Progression of exosome-mediated chemotherapy resistance in cancer. Oncologie, 2022, 24(2), 247-259.
[http://dx.doi.org/10.32604/oncologie.2022.020993]
[8]
Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478), eaau6977.
[http://dx.doi.org/10.1126/science.aau6977] [PMID: 32029601]
[9]
Li, M.Y.; Liu, L.Z.; Dong, M. Progress on pivotal role and application of exosome in lung cancer carcinogenesis, diagnosis, therapy and prognosis. Mol. Cancer, 2021, 20(1), 22.
[http://dx.doi.org/10.1186/s12943-021-01312-y] [PMID: 33504342]
[10]
Zhang, K.; Chen, J.; Li, C.; Yuan, Y.; Fang, S.; Liu, W.; Qian, Y.; Ma, J.; Chang, L.; Chen, F.; Yang, Z.; Gu, W. Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma. Cancer Lett., 2022, 526, 142-154.
[http://dx.doi.org/10.1016/j.canlet.2021.10.029] [PMID: 34715254]
[11]
Yu, Z.; Tang, H.; Chen, S.; Xie, Y.; Shi, L.; Xia, S.; Jiang, M.; Li, J.; Chen, D. Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist. Updat., 2023, 67, 100915.
[http://dx.doi.org/10.1016/j.drup.2022.100915] [PMID: 36641841]
[12]
Zhang, W.; Bai, M.; Liu, K.; Tan, J.; Ma, J.; Zhao, J.; Hou, P. LncRNA surfactant associated 1 activates large tumor suppressor kinase 1/Yes-associated protein pathway via modulating hypoxic exosome-delivered miR-4766–5p to inhibit lung adenocarcinoma metastasis. Int. J. Biochem. Cell Biol., 2022, 153, 106317.
[http://dx.doi.org/10.1016/j.biocel.2022.106317] [PMID: 36283586]
[13]
Chan, J.; Tay, Y. Noncoding RNA:RNA regulatory networks in cancer. Int. J. Mol. Sci., 2018, 19(5), 1310.
[http://dx.doi.org/10.3390/ijms19051310] [PMID: 29702599]
[14]
Wang, L.; Cho, K.B.; Li, Y.; Tao, G.; Xie, Z.; Guo, B. Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int. J. Mol. Sci., 2019, 20(22), 5758.
[http://dx.doi.org/10.3390/ijms20225758] [PMID: 31744051]
[15]
Shuwen, H.; Qing, Z.; Yan, Z.; Xi, Y. Competitive endogenous RNA in colorectal cancer: A systematic review. Gene, 2018, 645, 157-162.
[http://dx.doi.org/10.1016/j.gene.2017.12.036] [PMID: 29273554]
[16]
Li, Y.; Yu, X.; Zhang, Y.; Wang, X.; Zhao, L.; Liu, D.; Zhao, G.; Gao, X.; Fu, J.; Zang, A.; Jia, Y. Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis. Biomed. Eng. Online, 2021, 20(1), 117.
[http://dx.doi.org/10.1186/s12938-021-00952-x] [PMID: 34819106]
[17]
Wu, X.; Sui, Z.; Zhang, H.; Wang, Y.; Yu, Z. Integrated analysis of lncRNA–Mediated ceRNA network in lung adenocarcinoma. Front. Oncol., 2020, 10, 554759.
[http://dx.doi.org/10.3389/fonc.2020.554759] [PMID: 33042838]
[18]
Shen, W.; Song, Z.; Zhong, X.; Huang, M.; Shen, D.; Gao, P.; Qian, X.; Wang, M.; He, X.; Wang, T.; Li, S.; Song, X. Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform. iMeta, 2022, 1(3), e36.
[http://dx.doi.org/10.1002/imt2.36]
[19]
Wilkerson, M.D.; Hayes, D.N. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics, 2010, 26(12), 1572-1573.
[http://dx.doi.org/10.1093/bioinformatics/btq170] [PMID: 20427518]
[20]
Shah, S.N.A.; Parveen, R. An extensive review on lung cancer diagnosis using machine learning techniques on radiological data: State-of-the-art and perspectives. Arch. Comput. Methods Eng., 2023, 30(8), 4917-4930.
[http://dx.doi.org/10.1007/s11831-023-09964-3]
[21]
Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res., 2015, 43(7), e47.
[http://dx.doi.org/10.1093/nar/gkv007] [PMID: 25605792]
[22]
Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504.
[http://dx.doi.org/10.1101/gr.1239303] [PMID: 14597658]
[23]
Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[24]
Therneau, T.M.; Lumley, T. Package ‘survival’. R Top Doc, 2015, 128(10), 28-33.
[25]
Simon, N.; Friedman, J.; Hastie, T.; Tibshirani, R. Regularization paths for Cox’s proportional hazards model via coordinate descent. J. Stat. Softw., 2011, 39(5), 1-13.
[http://dx.doi.org/10.18637/jss.v039.i05] [PMID: 27065756]
[26]
Ripley, B. Package ‘mass’. Cran r, 2013, 538, 113-120.
[27]
Li, T.; Fan, J.; Wang, B.; Traugh, N.; Chen, Q.; Liu, J.S.; Li, B.; Liu, X.S. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res., 2017, 77(21), e108-e110.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[28]
Ru, B.; Wong, C.N.; Tong, Y.; Zhong, J.Y.; Zhong, S.S.W.; Wu, W.C.; Chu, K.C.; Wong, C.Y.; Lau, C.Y.; Chen, I.; Chan, N.W.; Zhang, J. TISIDB: an integrated repository portal for tumor–immune system interactions. Bioinformatics, 2019, 35(20), 4200-4202.
[http://dx.doi.org/10.1093/bioinformatics/btz210] [PMID: 30903160]
[29]
Aryee, M.J.; Jaffe, A.E.; Corrada-Bravo, H.; Ladd-Acosta, C.; Feinberg, A.P.; Hansen, K.D.; Irizarry, R.A. Minfi: a flexible and comprehensive bioconductor package for the analysis of infinium DNA methylation microarrays. Bioinformatics, 2014, 30(10), 1363-1369.
[http://dx.doi.org/10.1093/bioinformatics/btu049] [PMID: 24478339]
[30]
Chen, Y.; Wu, H.; Jiao, A.; Tong, J.; Zhu, J.; Zhang, M.; Li, Z.; Li, P. Chinese herbal prescription QYSL prevents progression of lung cancer by targeting tumor microenvironment. Oncologie, 2022, 24(2), 295-307.
[http://dx.doi.org/10.32604/oncologie.2022.022116]
[31]
Lang, Y.; Xu, S.; Ma, J.; Wu, J.; Jin, S.; Cao, S.; Yu, Y. MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes. Biochem. Biophys. Res. Commun., 2014, 450(1), 154-159.
[http://dx.doi.org/10.1016/j.bbrc.2014.05.084] [PMID: 24866238]
[32]
Wang, J.; Lai, X.; Peng, X. CircLIFR inhibits non-small cell lung cancer progression by acting as a miR-429 sponge to enhance CELF2 expression. Biochem. Genet., 2023, 61(2), 725-741.
[http://dx.doi.org/10.1007/s10528-022-10285-6] [PMID: 36104590]
[33]
Zhang, C.W.; Zhou, B.; Liu, Y.C.; Su, L.W.; Meng, J.; Li, S.L.; Wang, X.L. LINC00365 inhibited lung adenocarcinoma progression and glycolysis via sponging MIR -429/KCTD12 axis. Environ. Toxicol., 2022, 37(8), 1853-1866.
[http://dx.doi.org/10.1002/tox.23532] [PMID: 35426242]
[34]
Liang, R.; Xiao, G.; Wang, M.; Li, X.; Li, Y.; Hui, Z.; Sun, X.; Qin, S.; Zhang, B.; Du, N.; Liu, D.; Ren, H. SNHG6 functions as a competing endogenous RNA to regulate E2F7 expression by sponging miR-26a-5p in lung adenocarcinoma. Biomed. Pharmacother., 2018, 107, 1434-1446.
[http://dx.doi.org/10.1016/j.biopha.2018.08.099] [PMID: 30257360]
[35]
Chen, C.; Guo, Q.; Song, Y.; Xu, G.; Liu, L. SKA1/2/3 serves as a biomarker for poor prognosis in human lung adenocarcinoma. Transl. Lung Cancer Res., 2020, 9(2), 218-231.
[http://dx.doi.org/10.21037/tlcr.2020.01.20] [PMID: 32420061]
[36]
Li, Z.; Zhang, Y.; Zhou, Y.; Wang, F.; Yin, C.; Ding, L.; Zhang, S. Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway. Sci. Rep., 2021, 11(1), 23681.
[http://dx.doi.org/10.1038/s41598-021-03166-2] [PMID: 34880385]
[37]
Deng, B.; Chen, X.; Xu, L.; Zheng, L.; Zhu, X.; Shi, J.; Yang, L.; Wang, D.; Jiang, D. Chordin-like 1 is a novel prognostic biomarker and correlative with immune cell infiltration in lung adenocarcinoma. Aging (Albany NY), 2022, 14(1), 389-409.
[http://dx.doi.org/10.18632/aging.203814] [PMID: 35021154]
[38]
Ahmad, S.; Raza, K. Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study. Mol. Divers., 2023.
[http://dx.doi.org/10.1007/s11030-023-10648-0] [PMID: 37058176]
[39]
Ahmad, S.; Singh, V.; Gautam, H.K.; Raza, K. Multisampling-based docking reveals Imidazolidinyl urea as a multitargeted inhibitor for lung cancer: an optimisation followed multi-simulation and in-vitro study. J. Biomol. Struct. Dyn., 2023, 1-18.
[http://dx.doi.org/10.1080/07391102.2023.2209673] [PMID: 37154501]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy