Construction and Analysis of mRNA and lncRNA Regulatory Networks Reveal the Key Genes Associated with Prostate Cancer Related Fatigue During Localized Radiation Therapy

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Abstract

Background: Localized radiation therapy is the first-line option for the treatment of nonmetastatic prostate cancer (PCa). Previous studies revealed that long non-coding RNAs (lncRNAs) had crucial roles in disease progression. However, the mechanisms of lncRNAs underlying prostate cancerrelated fatigue remained largely unclear.

Objective: The present study aimed to uncover the key genes related to PCa related fatigue during localized radiation therapy by constructing mRNA and lncRNA regulatory networks.

Methods: We analyzed GSE30174, which included 10 control samples and 40 PCa related fatigue samples, to identify differently expressed lncRNAs and mRNAs in PCa related fatigue. A proteinprotein interaction network was constructed to reveal the interactions among mRNAs. Co-expression network analysis was applied to identify the key lncRNAs and reveal the functions of these lncRNAs in PCa related fatigue.

Results and Discussion: This research found 1271 dysregulated mRNAs and 205 dysregulated lncRNAs in PCa related fatigue using GSE30174. Bioinformatics analysis showed that PCa related fatigue with mRNAs and lncRNAs were associated with inflammatory response and immune response related biological processes. Furthermore, we constructed a PPI network and lncRNA co-expression network related to fatigue in PCa. Of note, we observed that the dysregulated lncRNAs and mRNAs, such as SEC61A2, ADCY6, LPAR5, COL7A1, ALB, COL1A1, SNHG1, LINC01215, LINC00926, GNG4, LMO7, and COL4A6, in PCa related fatigue could predict the outcome of PCa patients.

Conclusions: This research could provide novel mechanisms underlying fatigue and identify new biomarkers for the prognosis of PCa.

Keywords: Long non-coding RNAs, prostate cancer, fatigue, biomarker, co-expression analysis, genes.

Graphical Abstract

[1]
Viswanathan SR, Ha G, Hoff AM, et al. Structural alterations driving castration-resistant prostate cancer revealed by linked-read genome sequencing. Cell 2018; 174: 433-47.
[http://dx.doi.org/10.1016/j.cell.2018.05.036]
[2]
Robinson D, Van Allen EM, Wu YM, et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015; 161(5): 1215-28.
[http://dx.doi.org/10.1016/j.cell.2015.05.001] [PMID: 26000489]
[3]
Morgan SC, Hoffman K, Loblaw DA, et al. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline. J Urol 2018.S0022- 5347(18)43963-8.
[PMID: 30316897]
[4]
Huang H, Muscatelli S, Naslund M, Badiyan SN, Kaiser A, Siddiqui MM. Evaluation of cancer-specific mortality with surgery versus radiation as primary therapy for localized high-grade prostate cancer in men younger than 60 years. J Urol 2019; 201: 120-8.
[5]
Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 2014; 11(10): 597-609.
[http://dx.doi.org/10.1038/nrclinonc.2014.127] [PMID: 25113839]
[6]
Kamath J. Cancer-related fatigue, inflammation and thyrotropin-releasing hormone. Curr Aging Sci 2012; 5(3): 195-202.
[http://dx.doi.org/10.2174/1874609811205030005] [PMID: 23387883]
[7]
Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer 2018; 18(1): 5-18.
[http://dx.doi.org/10.1038/nrc.2017.99] [PMID: 29170536]
[8]
Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet 2001; 2(12): 919-29.
[http://dx.doi.org/10.1038/35103511] [PMID: 11733745]
[9]
Koch L. Functional genomics: Screening for lncRNA function. Nat Rev Genet 2017; 18(2): 70.
[PMID: 28045101]
[10]
Dickson I. Hepatocellular carcinoma: A role for lncRNA in liver cancer. Nat Rev Gastroenterol Hepatol 2016; 13(3): 122-3.
[PMID: 26860270]
[11]
Bai YH, Lv Y, Wang WQ, Sun GL, Zhang HH. LncRNA NEAT1 promotes inflammatory response and induces corneal neovascularization. J Mol Endocrinol 2018; 61(4): 231-9.
[http://dx.doi.org/10.1530/JME-18-0098] [PMID: 30328354]
[12]
Jiang M, Zhang S, Yang Z, et al. Self-recognition of an inducible host lncRNA by RIG-I feedback restricts innate immune response cell 2018; 173: 906-19.
[http://dx.doi.org/10.1016/j.cell.2018.03.064]
[13]
Saligan LN, Hsiao CP, Wang D, et al. Upregulation of α-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways. Brain Behav Immun 2013; 27(1): 63-70.
[http://dx.doi.org/10.1016/j.bbi.2012.09.009] [PMID: 23022913]
[14]
Piper BF, Dibble SL, Dodd MJ, Weiss MC, Slaughter RE, Paul SM. The revised Piper Fatigue Scale: psychometric evaluation in women with breast cancer. Oncol Nurs Forum 1998; 25(4): 677-84.
[PMID: 9599351]
[15]
Ritchie ME, Phipson B, Wu D, et al. 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]
[16]
Diboun I, Wernisch L, Orengo CA, Koltzenburg M. Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics 2006; 7: 252.
[http://dx.doi.org/10.1186/1471-2164-7-252] [PMID: 17029630]
[17]
Page RD. TreeView Glasgow University, Glasgow, UK2001.
[18]
Jensen LJ, Kuhn M, Stark M, et al. STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 2009; 37(Database issue): D412-6.
[http://dx.doi.org/10.1093/nar/gkn760] [PMID: 18940858]
[19]
Naorem LD, Muthaiyan M, Venkatesan A. Integrated network analysis and machine learning approach for the identification of key genes of triple-negative breast cancer. J Cell Biochem 2019; 120(4): 6154-67.
[http://dx.doi.org/10.1002/jcb.27903] [PMID: 30302816]
[20]
Tu Y, Fan G, Xi H, et al. Identification of candidate aberrantly methylated and differentially expressed genes in thyroid cancer. J Cell Biochem 2018; 119(11): 8797-806.
[http://dx.doi.org/10.1002/jcb.27129] [PMID: 30069928]
[21]
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.
[http://dx.doi.org/10.1093/nar/gkx247] [PMID: 28407145]
[22]
Zhang Y, Pitchiaya S, Cieślik M, et al. Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression. Nat Genet 2018; 50(6): 814-24.
[http://dx.doi.org/10.1038/s41588-018-0120-1] [PMID: 29808028]
[23]
Chakravarty D, Sboner A, Nair SS, et al. The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nat Commun 2014; 5: 5383.
[http://dx.doi.org/10.1038/ncomms6383] [PMID: 25415230]
[24]
Wan B, Wu HY, Lv DJ, et al. Downregulation of lncRNA PVT1 expression inhibits proliferation and migration by regulating p38 expression in prostate cancer. Oncol Lett 2018; 16(4): 5160-6.
[http://dx.doi.org/10.3892/ol.2018.9305] [PMID: 30250582]
[25]
Wan X, Huang W, Yang S, et al. Identification of androgen-responsive lncRNAs as diagnostic and prognostic markers for prostate cancer. Oncotarget 2016; 7(37): 60503-18.
[http://dx.doi.org/10.18632/oncotarget.11391] [PMID: 27556357]
[26]
Xu M, Chen X, Lin K, et al. The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p. Mol Cancer 2018; 17(1): 141.
[http://dx.doi.org/10.1186/s12943-018-0894-x] [PMID: 30266084]
[27]
Lu Q, Shan S, Li Y, Zhu D, Jin W, Ren T. Long noncoding RNA SNHG1 promotes non-small cell lung cancer progression by up-regulating MTDH via sponging miR-145-5p. FASEB J 2018; 32(7): 3957-67.
[http://dx.doi.org/10.1096/fj.201701237RR] [PMID: 29466052]
[28]
Li J, Zhang Z, Xiong L, et al. SNHG1 lncRNA negatively regulates miR-199a-3p to enhance CDK7 expression and promote cell proliferation in prostate cancer. Biochem Biophys Res Commun 2017; 487(1): 146-52.
[http://dx.doi.org/10.1016/j.bbrc.2017.03.169] [PMID: 28400279]
[29]
Cao B, Wang T, Qu Q, Kang T, Yang Q. Long noncoding RNA SNHG1 promotes neuroinflammation in Parkinson’s disease via regulating miR-7/NLRP3 pathway. Neuroscience 2018; 388: 118-27.
[http://dx.doi.org/10.1016/j.neuroscience.2018.07.019] [PMID: 30031125]
[30]
Xue D, Zhou C, Lu H, Xu R, Xu X, He X. LncRNA GAS5 inhibits proliferation and progression of prostate cancer by targeting miR-103 through AKT/mTOR signaling pathway. Tumour Biol 2016.
[http://dx.doi.org/10.1007/s13277-016-5429-8] [PMID: 27743383]
[31]
Pickard MR, Mourtada-Maarabouni M, Williams GT. Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta 2013; 1832(10): 1613-23.
[http://dx.doi.org/10.1016/j.bbadis.2013.05.005] [PMID: 23676682]
[32]
Zhang Y, Su X, Kong Z, et al. An androgen reduced transcript of LncRNA GAS5 promoted prostate cancer proliferation. PLoS One 2017; 12(8), e0182305.
[http://dx.doi.org/10.1371/journal.pone.0182305] [PMID: 28771526]