Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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

Bioinformatics Analysis of Autophagy-related lncRNAs in Esophageal Carcinoma

Author(s): Dan Wu, Yi Ding and JunBai Fan*

Volume 25, Issue 8, 2022

Published on: 24 June, 2021

Page: [1374 - 1384] Pages: 11

DOI: 10.2174/1386207324666210624143452

Price: $65

Abstract

Background: Esophageal carcinoma (ESCA) is a malignant tumor with high invasiveness and mortality. Autophagy has multiple roles in the development of cancer; however, there are limited data on autophagy genes associated with long non-coding RNAs (lncRNAs) in ESCA. The purpose of this study was to screen potential diagnostic and prognostic molecules and to identify gene co-expression networks associated with autophagy in ESCA.

Methods: We downloaded transcriptome expression profiles from The Cancer Genome Atlas and autophagy-related gene data from the Human Autophagy Database, and analyzed the co-expression of mRNAs and lncRNAs. In addition, the diagnostic and prognostic value of autophagy-related lncRNAs was analyzed by multivariate Cox regression. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was carried out for high-risk patients, and enriched pathways were analyzed by gene set enrichment analysis.

Results: The results showed that genes of high-risk patients were enriched in protein export and spliceosome. Based on Cox stepwise regression and survival analysis, we identified seven autophagy-related lncRNAs with prognostic and diagnostic value, with the potential to be used as a combination to predict the prognosis of patients with ESCA. Finally, a co-expression network related to autophagy was constructed.

Conclusion: These results suggest that autophagy-related lncRNAs and the spliceosome play important parts in the pathogenesis of ESCA. Our findings provide new insight into the molecular mechanism of ESCA and suggest a new method for improving its treatment.

Keywords: Autophagy, bioinformatics analysis, esophageal carcinoma, lncRNAs, mRNA, mortality.

« Previous Next »
[1]
Liu, G.; Pei, F.; Yang, F.; Li, L.; Amin, A.D.; Liu, S.; Buchan, J.R.; Cho, W.C. Role of autophagy and apoptosis in non-small-cell lung cancer. Int. J. Mol. Sci., 2017, 18(2), 18.
[http://dx.doi.org/10.3390/ijms18020367] [PMID: 28208579]
[2]
Poillet-Perez, L.; White, E. Role of tumor and host autophagy in cancer metabolism. Genes Dev., 2019, 33(11-12), 610-619.
[http://dx.doi.org/10.1101/gad.325514.119] [PMID: 31160394]
[3]
Levy, J.M.M.; Towers, C.G.; Thorburn, A. Targeting autophagy in cancer. Nat. Rev. Cancer, 2017, 17(9), 528-542.
[http://dx.doi.org/10.1038/nrc.2017.53] [PMID: 28751651]
[4]
Huang, T.; Song, X.; Yang, Y.; Wan, X.; Alvarez, A.A.; Sastry, N.; Feng, H.; Hu, B.; Cheng, S.Y. Autophagy and hallmarks of cancer. Crit. Rev. Oncog., 2018, 23(5-6), 247-267.
[http://dx.doi.org/10.1615/CritRevOncog.2018027913] [PMID: 30311559]
[5]
Hall, T.M.; Tétreault, M.P.; Hamilton, K.E.; Whelan, K.A. Autophagy as a cytoprotective mechanism in esophageal squamous cell carcinoma. Curr. Opin. Pharmacol., 2018, 41, 12-19.
[http://dx.doi.org/10.1016/j.coph.2018.04.003] [PMID: 29677645]
[6]
Bollschweiler, E.; Plum, P.; Mönig, S.P.; Hölscher, A.H. Current and future treatment options for esophageal cancer in the elderly. Expert Opin. Pharmacother., 2017, 18(10), 1001-1010.
[http://dx.doi.org/10.1080/14656566.2017.1334764] [PMID: 28540761]
[7]
Langer, R.; Streutker, C.J.; Swanson, P.E. Autophagy and its current relevance to the diagnosis and clinical management of esophageal diseases. Ann. N. Y. Acad. Sci., 2016, 1381(1), 113-121.
[http://dx.doi.org/10.1111/nyas.13190] [PMID: 27526024]
[8]
Saxena, R.; Klochkova, A.; Murray, M.G.; Kabir, M.F.; Samad, S.; Beccari, T.; Gang, J.; Patel, K.; Hamilton, K.E.; Whelan, K.A. Roles for autophagy in esophageal carcinogenesis: Implications for improving patient outcomes. Cancers (Basel), 2019, 11(11), 11.
[http://dx.doi.org/10.3390/cancers11111697] [PMID: 31683722]
[9]
Chen, H.I.; Tsai, H.P.; Chen, Y.T.; Tsao, S.C.; Chai, C.Y. Autophagy and apoptosis play opposing roles in overall survival of esophageal squamous cell carcinoma. Pathol. Oncol. Res., 2016, 22(4), 699-705.
[http://dx.doi.org/10.1007/s12253-016-0051-z] [PMID: 26980476]
[10]
Mao, Y.; Fu, Z.; Zhang, Y.; Dong, L.; Zhang, Y.; Zhang, Q.; Li, X.; Liu, J. A seven-lncRNA signature predicts overall survival in esophageal squamous cell carcinoma. Sci. Rep., 2018, 8(1), 8823.
[http://dx.doi.org/10.1038/s41598-018-27307-2] [PMID: 29891973]
[11]
Abdul Rahim, S.A.; Dirkse, A.; Oudin, A.; Schuster, A.; Bohler, J.; Barthelemy, V.; Muller, A.; Vallar, L.; Janji, B.; Golebiewska, A.; Niclou, S.P. Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A. Br. J. Cancer, 2017, 117(6), 813-825.
[http://dx.doi.org/10.1038/bjc.2017.263] [PMID: 28797031]
[12]
Yi, Y.; Liu, Y.; Wu, W.; Wu, K.; Zhang, W. Reconstruction and analysis of circRNA miRNA mRNA network in the pathology of cervical cancer. Oncol. Rep., 2019, 41(4), 2209-2225.
[http://dx.doi.org/10.3892/or.2019.7028] [PMID: 30816541]
[13]
Ludwig, N.; Fehlmann, T.; Kern, F.; Gogol, M.; Maetzler, W.; Deutscher, S.; Gurlit, S.; Schulte, C.; von Thaler, A.K.; Deuschle, C.; Metzger, F.; Berg, D.; Suenkel, U.; Keller, V.; Backes, C.; Lenhof, H.P.; Meese, E.; Keller, A. Machine learning to detect Alzheimer’s disease from circulating non-coding RNAs. Genomics Proteomics Bioinformatics, 2019, 17(4), 430-440.
[http://dx.doi.org/10.1016/j.gpb.2019.09.004] [PMID: 31809862]
[14]
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]
[15]
Liberzon, A.; Birger, C.; Thorvaldsdóttir, H.; Ghandi, M.; Mesirov, J.P.; Tamayo, P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst., 2015, 1(6), 417-425.
[http://dx.doi.org/10.1016/j.cels.2015.12.004] [PMID: 26771021]
[16]
Li, Z.; Dong, K.; Guo, P.; Tan, Z.; Zhang, F.; Tian, Y.; Lv, H. Identification of autophagy-related genes and small-molecule drugs in esophageal carcinoma. Med. Sci. Monit., 2020, 26e921855
[http://dx.doi.org/10.12659/MSM.921855] [PMID: 32415055]
[17]
Whelan, K.A.; Chandramouleeswaran, P.M.; Tanaka, K.; Natsuizaka, M.; Guha, M.; Srinivasan, S.; Darling, D.S.; Kita, Y.; Natsugoe, S.; Winkler, J.D.; Klein-Szanto, A.J.; Amaravadi, R.K.; Avadhani, N.G.; Rustgi, A.K.; Nakagawa, H. Autophagy supports generation of cells with high CD44 expression via modulation of oxidative stress and Parkin-mediated mitochondrial clearance. Oncogene, 2017, 36(34), 4843-4858.
[http://dx.doi.org/10.1038/onc.2017.102] [PMID: 28414310]
[18]
Khan, T.; Relitti, N.; Brindisi, M.; Magnano, S.; Zisterer, D.; Gemma, S.; Butini, S.; Campiani, G. Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas. Med. Res. Rev., 2020, 40(3), 1002-1060.
[http://dx.doi.org/10.1002/med.21646] [PMID: 31742748]
[19]
So, E.C.; Chen, Y.C.; Wang, S.C.; Wu, C.C.; Huang, M.C.; Lai, M.S.; Pan, B.S.; Kang, F.C.; Huang, B.M. Midazolam regulated caspase pathway, endoplasmic reticulum stress, autophagy, and cell cycle to induce apoptosis in MA-10 mouse Leydig tumor cells. OncoTargets Ther., 2016, 9, 2519-2533.
[PMID: 27175086]
[20]
Zhang, J.; Zhu, S.; Tan, Q.; Cheng, D.; Dai, Q.; Yang, Z.; Zhang, L.; Li, F.; Zuo, Y.; Dai, W.; Chen, L.; Gu, E.; Xu, G.; Wei, Z.; Cao, Y.; Liu, X. Combination therapy with ropivacaine-loaded liposomes and nutrient deprivation for simultaneous cancer therapy and cancer pain relief. Theranostics, 2020, 10(11), 4885-4899.
[http://dx.doi.org/10.7150/thno.43932] [PMID: 32308756]
[21]
Hsu, T.Y.; Simon, L.M.; Neill, N.J.; Marcotte, R.; Sayad, A.; Bland, C.S.; Echeverria, G.V.; Sun, T.; Kurley, S.J.; Tyagi, S.; Karlin, K.L.; Dominguez-Vidaña, R.; Hartman, J.D.; Renwick, A.; Scorsone, K.; Bernardi, R.J.; Skinner, S.O.; Jain, A.; Orellana, M.; Lagisetti, C.; Golding, I.; Jung, S.Y.; Neilson, J.R.; Zhang, X.H.; Cooper, T.A.; Webb, T.R.; Neel, B.G.; Shaw, C.A.; Westbrook, T.F. The spliceosome is a therapeutic vulnerability in MYC-driven cancer. Nature, 2015, 525(7569), 384-388.
[http://dx.doi.org/10.1038/nature14985] [PMID: 26331541]
[22]
Lee, S.C.; Abdel-Wahab, O. Therapeutic targeting of splicing in cancer. Nat. Med., 2016, 22(9), 976-986.
[http://dx.doi.org/10.1038/nm.4165] [PMID: 27603132]
[23]
Kidogami, S.; Iguchi, T.; Sato, K.; Yoshikawa, Y.; Hu, Q.; Nambara, S.; Komatsu, H.; Ueda, M.; Kuroda, Y.; Masuda, T.; Mori, M.; Doki, Y.; Mimori, K. SF3B4 plays an oncogenic role in esophageal squamous cell carcinoma. Anticancer Res., 2020, 40(5), 2941-2946.
[http://dx.doi.org/10.21873/anticanres.14272] [PMID: 32366446]
[24]
Hu, J.; Li, R.; Miao, H.; Wen, Z. Identification of key genes for esophageal squamous cell carcinoma via integrated bioinformatics analysis and experimental confirmation. J. Thorac. Dis., 2020, 12(6), 3188-3199.
[http://dx.doi.org/10.21037/jtd.2020.01.33] [PMID: 32642240]
[25]
Palrasu, M.; Knapinska, A.M.; Diez, J.; Smith, L.; LaVoi, T.; Giulianotti, M.; Houghten, R.A.; Fields, G.B.; Minond, D. A novel probe for spliceosomal proteins that induces autophagy and death of melanoma cells reveals new targets for melanoma drug discovery. Cell. Physiol. Biochem., 2019, 53(4), 656-686.
[http://dx.doi.org/10.33594/000000164] [PMID: 31573152]
[26]
Page, N.; Gros, F.; Schall, N.; Décossas, M.; Bagnard, D.; Briand, J.P.; Muller, S. HSC70 blockade by the therapeutic peptide P140 affects autophagic processes and endogenous MHCII presentation in murine lupus. Ann. Rheum. Dis., 2011, 70(5), 837-843.
[http://dx.doi.org/10.1136/ard.2010.139832] [PMID: 21173017]
[27]
Page, N.; Gros, F.; Schall, N.; Briand, J.P.; Muller, S. A therapeutic peptide in lupus alters autophagic processes and stability of MHCII molecules in MRL/lpr B cells. Autophagy, 2011, 7(5), 539-540.
[http://dx.doi.org/10.4161/auto.7.5.14845] [PMID: 21282971]
[28]
Quidville, V.; Alsafadi, S.; Goubar, A.; Commo, F.; Scott, V.; Pioche-Durieu, C.; Girault, I.; Baconnais, S.; Le Cam, E.; Lazar, V.; Delaloge, S.; Saghatchian, M.; Pautier, P.; Morice, P.; Dessen, P.; Vagner, S.; André, F. Targeting the deregulated spliceosome core machinery in cancer cells triggers mTOR blockade and autophagy. Cancer Res., 2013, 73(7), 2247-2258.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2501] [PMID: 23358685]
[29]
Martin, K.R.; Celano, S.L.; Solitro, A.R. A Potent and Selective ULK1 inhibitor suppresses autophagy and sensitizes cancer cells to nutrient stress. iScience, 2018, 8, 74-84.
[30]
Liu, J.; Long, S.; Wang, H.; Liu, N.; Zhang, C.; Zhang, L.; Zhang, Y. Blocking AMPK/ULK1-dependent autophagy promoted apoptosis and suppressed colon cancer growth. Cancer Cell Int., 2019, 19, 336.
[http://dx.doi.org/10.1186/s12935-019-1054-0] [PMID: 31871431]
[31]
Wang, L.; Wang, J.; Xiong, H.; Wu, F.; Lan, T.; Zhang, Y.; Guo, X.; Wang, H.; Saleem, M.; Jiang, C.; Lu, J.; Deng, Y. Co-targeting hexokinase 2-mediated Warburg effect and ULK1-dependent autophagy suppresses tumor growth of PTEN- and TP53-deficiency-driven castration-resistant prostate cancer. EBioMedicine, 2016, 7, 50-61.
[http://dx.doi.org/10.1016/j.ebiom.2016.03.022] [PMID: 27322458]
[32]
Jiang, S.; Li, Y.; Zhu, Y.H.; Wu, X.Q.; Tang, J.; Li, Z.; Feng, G.K.; Deng, R.; Li, D.D.; Luo, R.Z.; Zhang, M.F.; Qin, W.; Wang, X.; Jia, W.H.; Zhu, X.F. Intensive expression of UNC-51-like kinase 1 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Sci., 2011, 102(8), 1568-1575.
[http://dx.doi.org/10.1111/j.1349-7006.2011.01964.x] [PMID: 21518141]
[33]
He, W.; Wang, Q.; Xu, J.; Xu, X.; Padilla, M.T.; Ren, G.; Gou, X.; Lin, Y. Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation. Autophagy, 2012, 8(12), 1811-1821.
[http://dx.doi.org/10.4161/auto.22145] [PMID: 23051914]
[34]
Bao, Y.; Zhang, S.; Guo, Y.; Wei, X.; Zhang, Y.; Yang, Y.; Zhang, H.; Ma, M.; Yang, W. Stromal expression of JNK1 and VDR is associated with the prognosis of esophageal squamous cell carcinoma. Clin. Transl. Oncol., 2018, 20(9), 1185-1195.
[http://dx.doi.org/10.1007/s12094-018-1843-2] [PMID: 29423673]
[35]
Piqué, L.; Martinez de Paz, A.; Piñeyro, D.; Martínez-Cardús, A.; Castro de Moura, M.; Llinàs-Arias, P.; Setien, F.; Gomez-Miragaya, J.; Gonzalez-Suarez, E.; Sigurdsson, S.; Jonasson, J.G.; Villanueva, A.; Vidal, A.; Davalos, V.; Esteller, M. Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer. Oncogene, 2019, 38(45), 7106-7112.
[http://dx.doi.org/10.1038/s41388-019-0936-x] [PMID: 31409895]
[36]
Xu, G.; Li, T.; Chen, J.; Li, C.; Zhao, H.; Yao, C.; Dong, H.; Wen, K.; Wang, K.; Zhao, J.; Xia, Q.; Zhou, T.; Zhang, H.; Gao, P.; Li, A.; Pan, X. Autosomal dominant retinitis pigmentosa-associated gene PRPF8 is essential for hypoxia-induced mitophagy through regulating ULK1 mRNA splicing. Autophagy, 2018, 14(10), 1818-1830.
[http://dx.doi.org/10.1080/15548627.2018.1501251] [PMID: 30103670]
[37]
Yang, Y.H.; Markus, M.A.; Mangs, A.H.; Raitskin, O.; Sperling, R.; Morris, B.J. ZRANB2 localizes to supraspliceosomes and influences the alternative splicing of multiple genes in the transcriptome. Mol. Biol. Rep., 2013, 40(9), 5381-5395.
[http://dx.doi.org/10.1007/s11033-013-2637-9] [PMID: 23666063]
[38]
Dong, D.; Mu, Z.; Zhao, C.; Sun, M. ZFAS1: A novel tumor-related long non-coding RNA. Cancer Cell Int., 2018, 18, 125.
[http://dx.doi.org/10.1186/s12935-018-0623-y] [PMID: 30186041]
[39]
Chen, X.; Zeng, K.; Xu, M.; Hu, X.; Liu, X.; Xu, T.; He, B.; Pan, Y.; Sun, H.; Wang, S. SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis. Cell Death Dis., 2018, 9(10), 982.
[http://dx.doi.org/10.1038/s41419-018-0962-6] [PMID: 30250022]
[40]
Jiao, L.; Li, M.; Shao, Y.; Zhang, Y.; Gong, M.; Yang, X.; Wang, Y.; Tan, Z.; Sun, L.; Xuan, L.; Yu, Q.; Li, Y.; Gao, Y.; Liu, H.; Xu, H.; Li, X.; Zhang, Y.; Zhang, Y. lncRNA-ZFAS1 induces mitochondria-mediated apoptosis by causing cytosolic Ca2+ overload in myocardial infarction mice model. Cell Death Dis., 2019, 10(12), 942.
[http://dx.doi.org/10.1038/s41419-019-2136-6] [PMID: 31819041]
[41]
Li, Z.; Qin, X.; Bian, W.; Li, Y.; Shan, B.; Yao, Z.; Li, S. Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis. J. Exp. Clin. Cancer Res., 2019, 38(1), 477.
[http://dx.doi.org/10.1186/s13046-019-1473-8] [PMID: 31775815]
[42]
Li, T.; Wu, D.; Liu, Q.; Wang, D.; Chen, J.; Zhao, H.; Zhang, L.; Xie, C.; Zhu, W.; Chen, Z.; Zhou, Y.; Datta, S.; Qiu, F.; Yang, L.; Lu, J. Upregulation of long noncoding RNA RAB11B-AS1 promotes tumor metastasis and predicts poor prognosis in lung cancer. Ann. Transl. Med., 2020, 8(9), 582.
[http://dx.doi.org/10.21037/atm.2020.04.52] [PMID: 32566609]
[43]
Niu, Y.; Bao, L.; Chen, Y.; Wang, C.; Luo, M.; Zhang, B.; Zhou, M.; Wang, J.E.; Fang, Y.V.; Kumar, A.; Xing, C.; Wang, Y.; Luo, W. HIF2-Induced Long Noncoding RNA RAB11B-AS1 promotes hypoxia-mediated angiogenesis and breast cancer metastasis. Cancer Res., 2020, 80(5), 964-975.
[http://dx.doi.org/10.1158/0008-5472.CAN-19-1532] [PMID: 31900259]
[44]
Chen, Z.; Liu, Z.; Yang, Y.; Zhu, Z.; Liang, R.; Huang, B.; Wu, D.; Yang, L.; Lu, H.; Jin, D.; Li, Q. Long non-coding RNA RAB11B-AS1 prevents osteosarcoma development and progression via its natural antisense transcript RAB11B. Oncotarget, 2018, 9(42), 26770-26786.
[http://dx.doi.org/10.18632/oncotarget.24247] [PMID: 29928484]

Rights & Permissions Print Cite
Article Metrics
29
1
© 2024 Bentham Science Publishers | Privacy Policy