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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

An Autophagy-related Long Non-coding RNA Signature for Breast Cancer

Author(s): Feng Jiang, Chuyan Wu, Ming Wang, Ke Wei and Jimei Wang*

Volume 25, Issue 8, 2022

Published on: 17 August, 2021

Page: [1327 - 1335] Pages: 9

DOI: 10.2174/1386207324666210603122718

Price: $65

Abstract

Background: The most prevalent malignant tumor in women is breast cancer (BC). As autophagic therapies have been identified to contribute to BC cell death, the potential prognostic role of long non-coding RNA (lncRNA) related to autophagy in patients with BC was examined.

Methods: The lncRNAs expression profiles were derived from The Cancer Genome Atlas (TCGA) database. Throughout univariate Cox regression and multivariate Cox regression test, lncRNA with BC prognosis have been differentially presented. We then defined the optimal cut-off point between high and low-risk groups. The receiver operating characteristic (ROC) curves were drawn to test this signature. In order to examine possible signaling mechanisms linked to these lncRNAs, the Gene Set Enrichment Analysis (GSEA) has been carried out.

Results: Based on the lncRNA expression profiles for BC, a 9 lncRNA signature associated with autophagy was developed. The optimal cut-off value for high-risk and low-risk groups was used. The high-risk group had less survival time than the low-risk group. The result of this lncRNA signature was highly sensitive and precise. GSEA study found that the gene sets have been greatly enriched in many cancer pathways.

Conclusion: Our signature of 9 lncRNAs related to autophagy has prognostic value for BC, and these lncRNAs related to autophagy may play an important role in BC biology.

Keywords: Metastasis, breast cancer, prognosis, autophagy, long non-coding RNA, GSEA.

Graphical Abstract
[1]
Dumas, A.; Vaz Luis, I.; Bovagnet, T.; El Mouhebb, M.; Di Meglio, A.; Pinto, S.; Charles, C.; Dauchy, S.; Delaloge, S.; Arveux, P.; Coutant, C.; Cottu, P.; Lesur, A.; Lerebours, F.; Tredan, O.; Vanlemmens, L.; Levy, C.; Lemonnier, J.; Mesleard, C.; Andre, F.; Menvielle, G. Impact of Breast Cancer Treatment on Employment: Results of a Multicenter Prospective Cohort Study (CANTO). J. Clin. Oncol., 2020, 38(7), 734-743.
[http://dx.doi.org/10.1200/JCO.19.01726] [PMID: 31834818]
[2]
Afifi, A.M.; Saad, A.M.; Al-Husseini, M.J.; Elmehrath, A.O.; Northfelt, D.W.; Sonbol, M.B. Causes of death after breast cancer diagnosis: A US population-based analysis. Cancer, 2020, 126(7), 1559-1567.
[http://dx.doi.org/10.1002/cncr.32648] [PMID: 31840240]
[3]
Wang, T.; McCullough, L.E.; White, A.J.; Bradshaw, P.T.; Xu, X.; Cho, Y.H.; Terry, M.B.; Teitelbaum, S.L.; Neugut, A.I.; Santella, R.M.; Chen, J.; Gammon, M.D. Prediagnosis aspirin use, DNA methylation, and mortality after breast cancer: A population-based study. Cancer, 2019, 125(21), 3836-3844.
[http://dx.doi.org/10.1002/cncr.32364] [PMID: 31402456]
[4]
Clarke, M. Meta-analyses of adjuvant therapies for women with early breast cancer: the Early Breast Cancer Trialists’ Collaborative Group overview. Ann. Oncol., 2006, 17(Suppl. 10), x59-x62.
[http://dx.doi.org/10.1093/annonc/mdl238] [PMID: 17018753]
[5]
Curtis, C.; Shah, S.P.; Chin, S.F.; Turashvili, G.; Rueda, O.M.; Dunning, M.J.; Speed, D.; Lynch, A.G.; Samarajiwa, S.; Yuan, Y.; Gräf, S.; Ha, G.; Haffari, G.; Bashashati, A.; Russell, R.; McKinney, S.; Langerød, A.; Green, A.; Provenzano, E.; Wishart, G.; Pinder, S.; Watson, P.; Markowetz, F.; Murphy, L.; Ellis, I.; Purushotham, A.; Børresen-Dale, A.L.; Brenton, J.D.; Tavaré, S.; Caldas, C.; Aparicio, S. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 2012, 486(7403), 346-352.
[http://dx.doi.org/10.1038/nature10983] [PMID: 22522925]
[6]
Roulot, A.; Héquet, D.; Guinebretière, J.M.; Vincent-Salomon, A.; Lerebours, F.; Dubot, C.; Rouzier, R. Tumoral heterogeneity of breast cancer. Ann. Biol. Clin. (Paris), 2016, 74(6), 653-660.
[PMID: 27848916]
[7]
Valdora, F.; Houssami, N.; Rossi, F.; Calabrese, M.; Tagliafico, A.S. Rapid review: radiomics and breast cancer. Breast Cancer Res. Treat., 2018, 169(2), 217-229.
[http://dx.doi.org/10.1007/s10549-018-4675-4] [PMID: 29396665]
[8]
Sunkari, S.; Bonam, S.R.; Rao, A.V.S.; Riyaz, S.; Lakshma Nayak, V.; Kumar, H.M.S.; Kamal, A.; Nagendra Babu, B. Synthesis and biological evaluation of new bisindole-imidazopyridine hybrids as apoptosis inducers. Bioorg. Chem., 2019, 87, 484-494.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.061] [PMID: 30927589]
[9]
Moo, T.A.; Sanford, R.; Dang, C.; Morrow, M. Overview of breast cancer therapy. PET Clin., 2018, 13(3), 339-354.
[http://dx.doi.org/10.1016/j.cpet.2018.02.006] [PMID: 30100074]
[10]
Chen, Y.; Klionsky, D.J. The regulation of autophagy - unanswered questions. J. Cell Sci., 2011, 124(Pt 2), 161-170.
[http://dx.doi.org/10.1242/jcs.064576] [PMID: 21187343]
[11]
Kondratskyi, A.; Kondratska, K.; Skryma, R.; Klionsky, D.J.; Prevarskaya, N. Ion channels in the regulation of autophagy. Autophagy, 2018, 14(1), 3-21.
[http://dx.doi.org/10.1080/15548627.2017.1384887] [PMID: 28980859]
[12]
Zhou, B.; Liu, J.; Kang, R.; Klionsky, D.J.; Kroemer, G.; Tang, D. Ferroptosis is a type of autophagy-dependent cell death. Semin. Cancer Biol., 2019.
[http://dx.doi.org/10.1016/j.semcancer.2019.03.002] [PMID: 30880243]
[13]
He, C.; Klionsky, D.J. Regulation mechanisms and signaling pathways of autophagy. Annu. Rev. Genet., 2009, 43, 67-93.
[http://dx.doi.org/10.1146/annurev-genet-102808-114910] [PMID: 19653858]
[14]
Yang, Z.; Klionsky, D.J. An overview of the molecular mechanism of autophagy. Curr. Top. Microbiol. Immunol., 2009, 335, 1-32.
[http://dx.doi.org/10.1007/978-3-642-00302-8_1] [PMID: 19802558]
[15]
Rastaldo, R.; Vitale, E.; Giachino, C. Dual role of autophagy in regulation of mesenchymal stem cell senescence. Front. Cell Dev. Biol., 2020, 8, 276.
[http://dx.doi.org/10.3389/fcell.2020.00276] [PMID: 32391362]
[16]
Ren, Y.; Anaya-Eugenio, G.D.; Czarnecki, A.A.; Ninh, T.N.; Yuan, C.; Chai, H.B.; Soejarto, D.D.; Burdette, J.E.; de Blanco, E.J.C.; Kinghorn, A.D. Cytotoxic and NF-B and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives. Bioorg. Med. Chem., 2018, 26(15), 4452-4460.
[http://dx.doi.org/10.1016/j.bmc.2018.07.025] [PMID: 30057155]
[17]
Ren, Y.; Kinghorn, A.D. Natural product triterpenoids and their semi-synthetic derivatives with potential anticancer activity. Planta Med., 2019, 85(11-12), 802-814.
[http://dx.doi.org/10.1055/a-0832-2383] [PMID: 30658371]
[18]
Shen, C.; Ding, Y.; Tang, J.; Guo, F. Multivariate Information Fusion With Fast Kernel Learning to Kernel Ridge Regression in Predicting LncRNA-Protein Interactions. Front. Genet., 2019, 9, 716.
[http://dx.doi.org/10.3389/fgene.2018.00716] [PMID: 30697228]
[19]
Pang, D.; Hu, Q.; Lan, X.; Lin, Y.; Duan, H.; Cao, S.; Lin, Y.; Li, L.; Peng, F.; Pan, F. The novel long non coding RNA PRNCR1 2 is involved in breast cancer cell proliferation, migration, invasion and cell cycle progression. Mol. Med. Rep., 2019, 19(3), 1824-1832.
[PMID: 30592261]
[20]
Zhao, X.; Wang, P.; Liu, J.; Zheng, J.; Liu, Y.; Chen, J.; Xue, Y. Gas5 exerts tumor-suppressive functions in human glioma cells by targeting miR-222. Mol. Ther., 2015, 23(12), 1899-1911.
[http://dx.doi.org/10.1038/mt.2015.170] [PMID: 26370254]
[21]
Ji, J.; Dai, X.; Yeung, S.J.; He, X. The role of long non-coding RNA GAS5 in cancers. Cancer Manag. Res., 2019, 11, 2729-2737.
[http://dx.doi.org/10.2147/CMAR.S189052] [PMID: 31114330]
[22]
Formenti, S.C.; Arslan, A.A.; Love, S.M. Global breast cancer: the lessons to bring home. Int. J. Breast Cancer, 2012, 2012249501
[http://dx.doi.org/10.1155/2012/249501] [PMID: 22295243]
[23]
Surveillance report 2018 - Advanced breast cancer: Diagnosis and treatment (2009). NICE guideline CG81; National Institute for Health and Care Excellence: London, UK, 2018.
[24]
Li, M.H.; Fu, S.B.; Xiao, H.S. Genome-wide analysis of microRNA and mRNA expression signatures in cancer. Acta Pharmacol. Sin., 2015, 36(10), 1200-1211.
[http://dx.doi.org/10.1038/aps.2015.67] [PMID: 26299954]
[25]
Maycotte, P.; Jones, K.L.; Goodall, M.L.; Thorburn, J.; Thorburn, A. Autophagy supports breast cancer stem cell maintenance by regulating IL6 secretion. Mol. Cancer Res., 2015, 13(4), 651-658.
[http://dx.doi.org/10.1158/1541-7786.MCR-14-0487] [PMID: 25573951]
[26]
Qu, D.; Sun, W.W.; Li, L.; Ma, L.; Sun, L.; Jin, X.; Li, T.; Hou, W.; Wang, J.H. Long noncoding RNA MALAT1 releases epigenetic silencing of HIV-1 replication by displacing the polycomb repressive complex 2 from binding to the LTR promoter. Nucleic Acids Res., 2019, 47(6), 3013-3027.
[http://dx.doi.org/10.1093/nar/gkz117] [PMID: 30788509]
[27]
Carew, J.S.; Kelly, K.R.; Nawrocki, S.T. Autophagy as a target for cancer therapy: new developments. Cancer Manag. Res., 2012, 4, 357-365.
[PMID: 23091399]
[28]
Li, Y.; Cui, Y.; Wang, W.; Ma, M.; Li, M.; Chen, S. Effect of the Serum Inhibited Gene (Si1) on Autophagy and Apoptosis in MCF-7 Breast Cancer Cells. Cell. Physiol. Biochem., 2017, 41(6), 2268-2278.
[http://dx.doi.org/10.1159/000475644] [PMID: 28494449]
[29]
Wang, Z.; Han, W.; Sui, X.; Fang, Y.; Pan, H. Autophagy: A novel therapeutic target for hepatocarcinoma. (Review) Oncol. Lett., 2014, 7(5), 1345-1351. [Review].
[http://dx.doi.org/10.3892/2014.1916] [PMID: 24765136]
[30]
Jain, K.; Paranandi, K.S.; Sridharan, S.; Basu, A. Autophagy in breast cancer and its implications for therapy. Am. J. Cancer Res., 2013, 3(3), 251-265.
[PMID: 23841025]
[31]
Kondratskyi, A.; Yassine, M.; Kondratska, K.; Skryma, R.; Slomianny, C.; Prevarskaya, N. Calcium-permeable ion channels in control of autophagy and cancer. Front. Physiol., 2013, 4, 272.
[http://dx.doi.org/10.3389/fphys.2013.00272] [PMID: 24106480]
[32]
Shimizu, S. Autophagic Cell Death and Cancer Chemotherapeutics., 2015, 219
[http://dx.doi.org/10.1007/978-4-431-55651-0_18]
[33]
Chen, Y.J.; Fang, L.W.; Su, W.C.; Hsu, W.Y.; Yang, K.C.; Huang, H.L. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia. OncoTargets Ther., 2016, 9, 4453-4464.
[http://dx.doi.org/10.2147/OTT.S105664] [PMID: 27499639]
[34]
Lamark, T.; Kirkin, V.; Dikic, I.; Johansen, T. NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell Cycle, 2009, 8(13), 1986-1990.
[http://dx.doi.org/10.4161/cc.8.13.8892] [PMID: 19502794]
[35]
Lock, R.; Kenific, C.M.; Leidal, A.M.; Salas, E.; Debnath, J. Autophagy-dependent production of secreted factors facilitates oncogenic RAS-driven invasion. Cancer Discov., 2014, 4(4), 466-479.
[http://dx.doi.org/10.1158/2159-8290.CD-13-0841] [PMID: 24513958]
[36]
Pan, Y.; Pan, Y.; Cheng, Y.; Yang, F.; Yao, Z.; Wang, O. Knockdown of LncRNA MAPT-AS1 inhibites proliferation and migration and sensitizes cancer cells to paclitaxel by regulating MAPT expression in ER-negative breast cancers. Cell Biosci., 2018, 8, 7.
[http://dx.doi.org/10.1186/s13578-018-0207-5] [PMID: 29441192]
[37]
Pelechano, V.; Steinmetz, L.M. Gene regulation by antisense transcription. Nat. Rev. Genet., 2013, 14(12), 880-893.
[http://dx.doi.org/10.1038/nrg3594] [PMID: 24217315]
[38]
Huang, B.; Song, J.H.; Cheng, Y.; Abraham, J.M.; Ibrahim, S.; Sun, Z.; Ke, X.; Meltzer, S.J. Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression. Oncogene, 2016, 35(37), 4927-4936.
[http://dx.doi.org/10.1038/onc.2016.25] [PMID: 26876208]

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