Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

Hypoxia-induced Long Non-coding RNA LSAMP-AS1 Regulates ceRNA Network to Predict Prognosis for Pancreatic Cancer

Author(s): Lincheng Li, Wenbo Zou, Zhaohui Xiao, Zhaoda Deng and Rong Liu*

Volume 26, Issue 13, 2023

Published on: 11 April, 2023

Page: [2358 - 2371] Pages: 14

DOI: 10.2174/1386207326666230314112238

Price: $65

conference banner
Abstract

Background: The limited efficacy of chemotherapy and immunotherapy for pancreatic cancer is thought to be largely influenced by the surrounding cancer microenvironment. The hypoxic microenvironment caused by insufficient local blood supply is very important. However, the method to assess the level of hypoxia in the microenvironment of pancreatic cancer (PC) remains unclear.

Methods: In our research, we downloaded transcriptomic and clinicopathological data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A prognostic model was developed using univariate and multivariate Cox regression. The ConsensuClusterPlus R package was used to consistently cluster PC samples through unsupervised clustering. Gene set variation analysis (GSVA) was performed to identify the different functional phenotypes. The CIBERSORT evaluated the infiltration status of immune cells. qRT‐PCR was performed to detect the expression of genes in PC cells and tissues.

Results: A preliminary risk model was developed to reflect the hypoxic environment of pancreatic cancer. We found that a high hypoxia risk score indicated poor long-term survival and the presence of an immunosuppressive microenvironment. In addition, based on prognostic hypoxia-related genes, 177 PC samples were divided into two subtypes. Compared with cluster 2, cluster 1 was defined as the "hypoxic subgroup". The infiltration of CD8 T cells, activated memory CD4 T cells, naive B cells, memory B cells, plasma cells, and neutrophils were lower in cluster 1, suggesting that there was significant immunosuppression in cluster 1. Beyond that, we constructed a ceRNA regulatory network composed of differentially expressed lncRNA, miRNA, and mRNA. LSAMPAS1/ hsa-miR-129-5p/S100A2 has been identified as a key ceRNA network that regulates the hypoxic environment and the prognosis of PC. Notably, in our study, qRT-PCR revealed the relative expression of LSAMP-AS1 and S100A2 was significantly upregulated in PC cells and tissue.

Conclusion: The hypoxia-related prognostic risk model and core ceRNA network established in our study will provide a new perspective for exploring the carcinogenic mechanism and potential therapeutic targets of pancreatic cancer.

Graphical Abstract

[1]
Mizrahi, J.D.; Surana, R.; Valle, J.W.; Shroff, R.T. Pancreatic cancer. Lancet, 2020, 395(10242), 2008-2020.
[http://dx.doi.org/10.1016/S0140-6736(20)30974-0] [PMID: 32593337]
[2]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[3]
Morrison, A.H.; Byrne, K.T.; Vonderheide, R.H. Immunotherapy and prevention of pancreatic cancer. Trends Cancer, 2018, 4(6), 418-428.
[http://dx.doi.org/10.1016/j.trecan.2018.04.001] [PMID: 29860986]
[4]
Ilic, M.; Ilic, I. Epidemiology of pancreatic cancer. World J. Gastroenterol., 2016, 22(44), 9694-9705.
[http://dx.doi.org/10.3748/wjg.v22.i44.9694] [PMID: 27956793]
[5]
Dhani, N.; Fyles, A.; Hedley, D.; Milosevic, M. The clinical significance of hypoxia in human cancers. Semin. Nucl. Med., 2015, 45(2), 110-121.
[http://dx.doi.org/10.1053/j.semnuclmed.2014.11.002] [PMID: 25704384]
[6]
Bhandari, V.; Hoey, C.; Liu, L.Y.; Lalonde, E.; Ray, J.; Livingstone, J.; Lesurf, R.; Shiah, Y.J.; Vujcic, T.; Huang, X.; Espiritu, S.M.G.; Heisler, L.E.; Yousif, F.; Huang, V.; Yamaguchi, T.N.; Yao, C.Q.; Sabelnykova, V.Y.; Fraser, M.; Chua, M.L.K.; van der Kwast, T.; Liu, S.K.; Boutros, P.C.; Bristow, R.G. Molecular landmarks of tumor hypoxia across cancer types. Nat. Genet., 2019, 51(2), 308-318.
[http://dx.doi.org/10.1038/s41588-018-0318-2] [PMID: 30643250]
[7]
Teicher, B.A.; Lazo, J.S.; Sartorelli, A.C. Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res., 1981, 41(1), 73-81.
[PMID: 7448778]
[8]
Graham, K.; Unger, E. Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment. Int. J. Nano., 2018, 13, 6049-6058.
[http://dx.doi.org/10.2147/IJN.S140462] [PMID: 30323592]
[9]
Hatfield, S.M.; Kjaergaard, J.; Lukashev, D.; Schreiber, T.H.; Belikoff, B.; Abbott, R.; Sethumadhavan, S.; Philbrook, P.; Ko, K.; Cannici, R.; Thayer, M.; Rodig, S.; Kutok, J.L.; Jackson, E.K.; Karger, B.; Podack, E.R.; Ohta, A.; Sitkovsky, M.V. Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci. Transl. Med., 2015, 7(277), 277ra30.
[http://dx.doi.org/10.1126/scitranslmed.aaa1260] [PMID: 25739764]
[10]
Zhou, C.; Yi, C.; Yi, Y.; Qin, W.; Yan, Y.; Dong, X.; Zhang, X.; Huang, Y.; Zhang, R.; Wei, J.; Ali, D.W.; Michalak, M.; Chen, X.Z.; Tang, J. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes. Mol. Cancer, 2020, 19(1), 118.
[http://dx.doi.org/10.1186/s12943-020-01237-y] [PMID: 32727463]
[11]
Deng, S.; Chen, H.; Ye, Z.; Deng, S.; Zhu, S.; Zeng, Z.; He, C.; Liu, M.; Huang, K.; Zhong, J.; Xu, F.; Li, Q.; Liu, Y.; Wang, C.; Zhao, G. Hypoxia-induced LncRNA-BX111 promotes metastasis and progression of pancreatic cancer through regulating ZEB1 transcription. Oncogene, 2018, 37(44), 5811-5828.
[http://dx.doi.org/10.1038/s41388-018-0382-1] [PMID: 29970904]
[12]
Chen, B.; Deng, S.; Ge, T.; Ye, M.; Yu, J.; Lin, S.; Ma, W.; Songyang, Z. Live cell imaging and proteomic profiling of endogenous NEAT1 lncRNA by CRISPR/Cas9-mediated knock-in. Protein Cell, 2020, 11(9), 641-660.
[http://dx.doi.org/10.1007/s13238-020-00706-w] [PMID: 32458346]
[13]
Ding, J.N.; Zang, Y.F.; Ding, Y.L. MiRNA-146b-5p inhibits the malignant progression of gastric cancer by targeting TRAF6. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(17), 8837-8844.
[http://dx.doi.org/10.26355/eurrev_202009_22823] [PMID: 32964972]
[14]
Pidíkova, P.; Reis, R.; Herichova, I. miRNA clusters with down-regulated expression in human colorectal cancer and their regulation. Int. J. Mol. Sci., 2020, 21(13), 4633.
[http://dx.doi.org/10.3390/ijms21134633] [PMID: 32610706]
[15]
Han, T.S.; Hur, K.; Cho, H.S.; Ban, H.S. Epigenetic associations between lncRNA/circRNA and miRNA in hepatocellular carcinoma. Cancers, 2020, 12(9), 2622.
[http://dx.doi.org/10.3390/cancers12092622] [PMID: 32937886]
[16]
Zhang, H.; Zhu, C.; He, Z.; Chen, S.; Li, L.; Sun, C. LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis. J. Exp. Clin. Cancer Res., 2020, 39(1), 179.
[http://dx.doi.org/10.1186/s13046-020-01687-8] [PMID: 32891166]
[17]
Pereira, S.P.; Oldfield, L.; Ney, A.; Hart, P.A.; Keane, M.G.; Pandol, S.J.; Li, D.; Greenhalf, W.; Jeon, C.Y.; Koay, E.J.; Almario, C.V.; Halloran, C.; Lennon, A.M.; Costello, E. Early detection of pancreatic cancer. Lancet Gastroenterol. Hepatol., 2020, 5(7), 698-710.
[http://dx.doi.org/10.1016/S2468-1253(19)30416-9] [PMID: 32135127]
[18]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[19]
Allemani, C.; Matsuda, T.; Di Carlo, V.; Harewood, R.; Matz, M.; Nikšić, M.; Bonaventure, A.; Valkov, M.; Johnson, C.J.; Estève, J.; Ogunbiyi, O.J.; Azevedo e Silva, G.; Chen, W.Q.; Eser, S.; Engholm, G.; Stiller, C.A.; Monnereau, A.; Woods, R.R.; Visser, O.; Lim, G.H.; Aitken, J.; Weir, H.K.; Coleman, M.P.; Bouzbid, S.; Hamdi-Chérif, M.; Zaidi, Z.; Meguenni, K.; Regagba, D.; Bayo, S.; Cheick Bougadari, T.; Manraj, S.S.; Bendahhou, K.; Fabowale, A.; Bradshaw, D.; Somdyala, N.I.M.; Kumcher, I.; Moreno, F.; Calabrano, G.H.; Espinola, S.B.; Carballo Quintero, B.; Fita, R.; Diumenjo, M.C.; Laspada, W.D.; Ibañez, S.G.; Lima, C.A.; De Souza, P.C.F.; Del Pino, K.; Laporte, C.; Curado, M.P.; de Oliveira, J.C.; Veneziano, C.L.A.; Veneziano, D.B.; Latorre, M.R.D.O.; Tanaka, L.F.; Rebelo, M.S.; Santos, M.O.; Galaz, J.C.; Aparicio Aravena, M.; Sanhueza Monsalve, J.; Herrmann, D.A.; Vargas, S.; Herrera, V.M.; Uribe, C.J.; Bravo, L.E.; Garcia, L.S.; Arias-Ortiz, N.E.; Morantes, D.; Jurado, D.M.; Yépez Chamorro, M.C.; Delgado, S.; Ramirez, M.; Galán Alvarez, Y.H.; Torres, P.; Martínez-Reyes, F.; Jaramillo, L.; Quinto, R.; Castillo, J.; Mendoza, M.; Cueva, P.; Yépez, J.G.; Bhakkan, B.; Deloumeaux, J.; Joachim, C.; Macni, J.; Carrillo, R.; Shalkow Klincovstein, J.; Rivera Gomez, R.; Poquioma, E.; Tortolero-Luna, G.; Zavala, D.; Alonso, R.; Barrios, E.; Eckstrand, A.; Nikiforuk, C.; Noonan, G.; Turner, D.; Kumar, E.; Zhang, B.; McCrate, F.R.; Ryan, S.; MacIntyre, M.; Saint-Jacques, N.; Nishri, D.E.; McClure, C.A.; Vriends, K.A.; Kozie, S.; Stuart-Panko, H.; Freeman, T.; George, J.T.; Brockhouse, J.T.; O’Brien, D.K.; Holt, A.; Almon, L.; Kwong, S.; Morris, C.; Rycroft, R.; Mueller, L.; Phillips, C.E.; Brown, H.; Cromartie, B.; Schwartz, A.G.; Vigneau, F.; Levin, G.M.; Wohler, B.; Bayakly, R.; Ward, K.C.; Gomez, S.L.; McKinley, M.; Cress, R.; Green, M.D.; Miyagi, K.; Ruppert, L.P.; Lynch, C.F.; Huang, B.; Tucker, T.C.; Deapen, D.; Liu, L.; Hsieh, M.C.; Wu, X.C.; Schwenn, M.; Gershman, S.T.; Knowlton, R.C.; Alverson, G.; Copeland, G.E.; Bushhouse, S.; Rogers, D.B.; Jackson-Thompson, J.; Lemons, D.; Zimmerman, H.J.; Hood, M.; Roberts-Johnson, J.; Rees, J.R.; Riddle, B.; Pawlish, K.S.; Stroup, A.; Key, C.; Wiggins, C.; Kahn, A.R.; Schymura, M.J.; Radhakrishnan, S.; Rao, C.; Giljahn, L.K.; Slocumb, R.M.; Espinoza, R.E.; Khan, F.; Aird, K.G.; Beran, T.; Rubertone, J.J.; Slack, S.J.; Garcia, L.; Rousseau, D.L.; Janes, T.A.; Schwartz, S.M.; Bolick, S.W.; Hurley, D.M.; Whiteside, M.A.; Miller-Gianturco, P.; Williams, M.A.; Herget, K.; Sweeney, C.; Johnson, A.T.; Keitheri Cheteri, M.B.; Migliore Santiago, P.; Blankenship, S.E.; Farley, S.; Borchers, R.; Malicki, R.; Espinoza, J.R.; Grandpre, J.; Wilson, R.; Edwards, B.K.; Mariotto, A.; Lei, Y.; Wang, N.; Chen, J.S.; Zhou, Y.; He, Y.T.; Song, G.H.; Gu, X.P.; Mei, D.; Mu, H.J.; Ge, H.M.; Wu, T.H.; Li, Y.Y.; Zhao, D.L.; Jin, F.; Zhang, J.H.; Zhu, F.D.; Junhua, Q.; Yang, Y.L.; Jiang, C.X.; Biao, W.; Wang, J.; Li, Q.L.; Yi, H.; Zhou, X.; Dong, J.; Li, W.; Fu, F.X.; Liu, S.Z.; Chen, J.G.; Zhu, J.; Li, Y.H.; Lu, Y.Q.; Fan, M.; Huang, S.Q.; Guo, G.P.; Zhaolai, H.; Wei, K.; Zeng, H.; Demetriou, A.V.; Mang, W.K.; Ngan, K.C.; Kataki, A.C.; Krishnatreya, M.; Jayalekshmi, P.A.; Sebastian, P.; Nandakumar, A.; Malekzadeh, R.; Roshandel, G.; Keinan-Boker, L.; Silverman, B.G.; Ito, H.; Nakagawa, H.; Sato, M.; Tobori, F.; Nakata, I.; Teramoto, N.; Hattori, M.; Kaizaki, Y.; Moki, F.; Sugiyama, H.; Utada, M.; Nishimura, M.; Yoshida, K.; Kurosawa, K.; Nemoto, Y.; Narimatsu, H.; Sakaguchi, M.; Kanemura, S.; Naito, M.; Narisawa, R.; Miyashiro, I.; Nakata, K.; Sato, S.; Yoshii, M.; Oki, I.; Fukushima, N.; Shibata, A.; Iwasa, K.; Ono, C.; Nimri, O.; Jung, K.W.; Won, Y.J.; Alawadhi, E.; Elbasmi, A.; Ab Manan, A.; Adam, F.; Sanjaajmats, E.; Tudev, U.; Ochir, C.; Al Khater, A.M.; El Mistiri, M.M.; Teo, Y.Y.; Chiang, C.J.; Lee, W.C.; Buasom, R.; Sangrajrang, S.; Kamsa-ard, S.; Wiangnon, S.; Daoprasert, K.; Pongnikorn, D.; Leklob, A.; Sangkitipaiboon, S.; Geater, S.L.; Sriplung, H.; Ceylan, O.; Kög, I.; Dirican, O.; Köse, T.; Gurbuz, T.; Karaşahin, F.E.; Turhan, D.; Aktaş, U.; Halat, Y.; Yakut, C.I.; Altinisik, M.; Cavusoglu, Y.; Türkköylü, A.; Üçüncü, N.; Hackl, M.; Zborovskaya, A.A.; Aleinikova, O.V.; Henau, K.; Van Eycken, L.; Valerianova, Z.; Yordanova, M.R.; Šekerija, M.; Dušek, L.; Zvolský, M.; Storm, H.; Innos, K.; Mägi, M.; Malila, N.; Seppä, K.; Jégu, J.; Velten, M.; Cornet, E.; Troussard, X.; Bouvier, A.M.; Guizard, A.V.; Bouvier, V.; Launoy, G.; Arveux, P.; Maynadié, M.; Mounier, M.; Woronoff, A.S.; Daoulas, M.; Robaszkiewicz, M.; Clavel, J.; Goujon, S.; Lacour, B.; Baldi, I.; Pouchieu, C.; Amadeo, B.; Coureau, G.; Orazio, S.; Preux, P.M.; Rharbaoui, F.; Marrer, E.; Trétarre, B.; Colonna, M.; Delafosse, P.; Ligier, K.; Plouvier, S.; Cowppli-Bony, A.; Molinié, F.; Bara, S.; Ganry, O.; Lapôtre-Ledoux, B.; Grosclaude, P.; Bossard, N.; Uhry, Z.; Bray, F.; Piñeros, M.; Stabenow, R.; Wilsdorf-Köhler, H.; Eberle, A.; Luttmann, S.; Löhden, I.; Nennecke, A.L.; Kieschke, J.; Sirri, E.; Emrich, K.; Zeissig, S.R.; Holleczek, B.; Eisemann, N.; Katalinic, A.; Asquez, R.A.; Kumar, V.; Petridou, E.; Ólafsdóttir, E.J.; Tryggvadóttir, L.; Clough-Gorr, K.; Walsh, P.M.; Sundseth, H.; Mazzoleni, G.; Vittadello, F.; Coviello, E.; Cuccaro, F.; Galasso, R.; Sampietro, G.; Giacomin, A.; Magoni, M.; Ardizzone, A.; D’Argenzio, A.; Castaing, M.; Grosso, G.; Lavecchia, A.M.; Sutera Sardo, A.; Gola, G.; Gatti, L.; Ricci, P.; Ferretti, S.; Serraino, D.; Zucchetto, A.; Celesia, M.V.; Filiberti, R.A.; Pannozzo, F.; Melcarne, A.; Quarta, F.; Russo, A.G.; Carrozzi, G.; Cirilli, C.; Cavalieri d’Oro, L.; Rognoni, M.; Fusco, M.; Vitale, M.F.; Usala, M.; Cusimano, R.; Mazzucco, W.; Michiara, M.; Sgargi, P.; Boschetti, L.; Borciani, E.; Seghini, P.; Maule, M.M.; Merletti, F.; Tumino, R.; Mancuso, P.; Vicentini, M.; Cassetti, T.; Sassatelli, R.; Falcini, F.; Giorgetti, S.; Caiazzo, A.L.; Cavallo, R.; Cesaraccio, R.; Pirino, D.R.; Contrino, M.L.; Tisano, F.; Fanetti, A.C.; Maspero, S.; Carone, S.; Mincuzzi, A.; Candela, G.; Scuderi, T.; Gentilini, M.A.; Piffer, S.; Rosso, S.; Barchielli, A.; Caldarella, A.; Bianconi, F.; Stracci, F.; Contiero, P.; Tagliabue, G.; Rugge, M.; Zorzi, M.; Beggiato, S.; Brustolin, A.; Berrino, F.; Gatta, G.; Sant, M.; Buzzoni, C.; Mangone, L.; Capocaccia, R.; De Angelis, R.; Zanetti, R.; Maurina, A.; Pildava, S.; Lipunova, N.; Vincerževskiené, I.; Agius, D.; Calleja, N.; Siesling, S.; Larønningen, S.; Møller, B.; Dyzmann-Sroka, A.; Trojanowski, M.; Góźdź, S.; Mężyk, R.; Mierzwa, T.; Molong, L.; Rachtan, J.; Szewczyk, S.; Błaszczyk, J.; Kępska, K.; Kościańska, B.; Tarocińska, K.; Zwierko, M.; Drosik, K.; Maksimowicz, K.M.; Purwin-Porowska, E.; Reca, E.; Wójcik-Tomaszewska, J.; Tukiendorf, A.; Grądalska-Lampart, M.; Radziszewska, A.U.; Gos, A.; Talerczyk, M.; Wyborska, M.; Didkowska, J.A.; Wojciechowska, U.; Bielska-Lasota, M.; Forjaz de Lacerda, G.; Rego, R.A.; Bastos, J.; Silva, M.A.; Antunes, L.; Laranja Pontes, J.; Mayer-da-Silva, A.; Miranda, A.; Blaga, L.M.; Coza, D.; Gusenkova, L.; Lazarevich, O.; Prudnikova, O.; Vjushkov, D.M.; Egorova, A.G.; Orlov, A.E.; Kudyakov, L.A.; Pikalova, L.V.; Adamcik, J.; Safaei Diba, C.; Primic-Žakelj, M.; Zadnik, V.; Larrañaga, N.; Lopez de Munain, A.; Herrera, A.A.; Redondas, R.; Marcos-Gragera, R.; Vilardell Gil, M.L.; Molina, E.; Sánchez Perez, M.J.; Franch Sureda, P.; Ramos Montserrat, M.; Chirlaque, M.D.; Navarro, C.; Ardanaz, E.E.; Guevara, M.M.; Fernández-Delgado, R.; Peris-Bonet, R.; Carulla, M.; Galceran, J.; Alberich, C.; Vicente-Raneda, M.; Khan, S.; Pettersson, D.; Dickman, P.; Avelina, I.; Staehelin, K.; Camey, B.; Bouchardy, C.; Schaffar, R.; Frick, H.; Herrmann, C.; Bulliard, J.L.; Maspoli-Conconi, M.; Kuehni, C.E.; Redmond, S.M.; Bordoni, A.; Ortelli, L.; Chiolero, A.; Konzelmann, I.; Matthes, K.L.; Rohrmann, S.; Broggio, J.; Rashbass, J.; Fitzpatrick, D.; Gavin, A.; Clark, D.I.; Deas, A.J.; Huws, D.W.; White, C.; Montel, L.; Rachet, B.; Turculet, A.D.; Stephens, R.; Chalker, E.; Phung, H.; Walton, R.; You, H.; Guthridge, S.; Johnson, F.; Gordon, P.; D’Onise, K.; Priest, K.; Stokes, B.C.; Venn, A.; Farrugia, H.; Thursfield, V.; Dowling, J.; Currow, D.; Hendrix, J.; Lewis, C. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet, 2018, 391(10125), 1023-1075.
[http://dx.doi.org/10.1016/S0140-6736(17)33326-3] [PMID: 29395269]
[20]
Lu, Y.; Liu, Y.; Oeck, S.; Zhang, G.J.; Schramm, A.; Glazer, P.M. Hypoxia induces resistance to EGFR inhibitors in lung cancer cells via upregulation of FGFR1 and the MAPK pathway. Cancer Res., 2020, 80(21), 4655-4667.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-1192] [PMID: 32873635]
[21]
Wei, X.; Chen, Y.; Jiang, X.; Peng, M.; Liu, Y.; Mo, Y.; Ren, D.; Hua, Y.; Yu, B.; Zhou, Y.; Liao, Q.; Wang, H.; Xiang, B.; Zhou, M.; Li, X.; Li, G.; Li, Y.; Xiong, W.; Zeng, Z. Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol. Cancer, 2021, 20(1), 7.
[http://dx.doi.org/10.1186/s12943-020-01288-1] [PMID: 33397409]
[22]
Tao, J.; Yang, G.; Zhou, W.; Qiu, J.; Chen, G.; Luo, W.; Zhao, F.; You, L.; Zheng, L.; Zhang, T.; Zhao, Y. Targeting hypoxic tumor microenvironment in pancreatic cancer. J. Hematol. Oncol., 2021, 14(1), 14.
[http://dx.doi.org/10.1186/s13045-020-01030-w] [PMID: 33436044]
[23]
Qin, Y.; Zhu, W.; Xu, W.; Zhang, B.; Shi, S.; Ji, S.; Liu, J.; Long, J.; Liu, C.; Liu, L.; Xu, J.; Yu, X. LSD1 sustains pancreatic cancer growth via maintaining HIF1α-dependent glycolytic process. Cancer Lett., 2014, 347(2), 225-232.
[http://dx.doi.org/10.1016/j.canlet.2014.02.013] [PMID: 24561118]
[24]
Ding, J.; He, X.; Cheng, X.; Cao, G.; Chen, B.; Chen, S.; Xiong, M.A. 4-gene-based hypoxia signature is associated with tumor immune microenvironment and predicts the prognosis of pancreatic cancer patients. World J. Surg. Oncol., 2021, 19(1), 123.
[http://dx.doi.org/10.1186/s12957-021-02204-7] [PMID: 33865399]
[25]
Abou, K. R.; Rao, S. P.; Venkatesh, G. H.; Zeinelabdin, N. A.; Buart, S.; Meylan, M.; Nimmakayalu, M.; Terry, S.; Chouaib, S. An eight-gene hypoxia signature predicts survival in pancreatic cancer and is associated with an immunosuppressed tumor microenvironment. Front. Immunol., 2021, 12, 680435.
[http://dx.doi.org/10.3389/fimmu.2021.680435] [PMID: 34093582]
[26]
de Heer, E.C.; Jalving, M.; Harris, A.L. HIFs, angiogenesis, and metabolism: Elusive enemies in breast cancer. J. Clin. Invest., 2020, 130(10), 5074-5087.
[http://dx.doi.org/10.1172/JCI137552] [PMID: 32870818]
[27]
Yuen, V.W.H.; Wong, C.C.L. Hypoxia-inducible factors and innate immunity in liver cancer. J. Clin. Invest., 2020, 130(10), 5052-5062.
[http://dx.doi.org/10.1172/JCI137553] [PMID: 32750043]
[28]
Li, L.; Wang, Q.; Yuan, Z.; Chen, A.; Liu, Z.; Wang, Z.; Li, H. LncRNA-MALAT1 promotes CPC proliferation and migration in hypoxia by up-regulation of JMJD6 via sponging miR-125. Biochem. Biophys. Res. Commun., 2018, 499(3), 711-718.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.216] [PMID: 29605300]
[29]
Lee, Y.F.; Miller, L.D.; Chan, X.B.; Black, M.A.; Pang, B.; Ong, C.W.; Salto-Tellez, M.; Liu, E.T.; Desai, K.V. JMJD6 is a driver of cellular proliferation and motility and a marker of poor prognosis in breast cancer. Breast Cancer Res., 2012, 14(3), 3001.
[http://dx.doi.org/10.1186/bcr3200] [PMID: 22621393]
[30]
Chen, S.; Fang, X.Q.; Wang, Q.; Wang, S.W.; Hu, Z.J.; Zhou, Z.J.; Xu, W.B.; Wang, J.Y.; Qin, A.; Fan, S.W. PHD/HIF-1 upregulates CA12 to protect against degenerative disc disease: A human sample, in vitro and ex vivo study. Lab. Invest., 2016, 96(5), 561-569.
[http://dx.doi.org/10.1038/labinvest.2016.32] [PMID: 26901836]
[31]
Mao, X.; Wong, S.Y.S.; Tse, E.Y.T.; Ko, F.C.F.; Tey, S.K.; Yeung, Y.S.; Man, K.; Lo, R.C.L.; Ng, I.O.L.; Yam, J.W.P. Mechanisms through which hypoxia-induced caveolin-1 drives tumorigenesis and metastasis in hepatocellular carcinoma. Cancer Res., 2016, 76(24), 7242-7253.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1031] [PMID: 27784747]
[32]
Nonaka, M.; Fukuda, M.N.; Gao, C.; Li, Z.; Zhang, H.; Greene, M.I.; Peehl, D.M.; Feizi, T.; Fukuda, M. Determination of carbohydrate structure recognized by prostate-specific F77 monoclonal antibody through expression analysis of glycosyltransferase genes. J. Biol. Chem., 2014, 289(23), 16478-16486.
[http://dx.doi.org/10.1074/jbc.M114.559047] [PMID: 24753248]
[33]
Ma, B.; Chen, Y.; Chen, L.; Cheng, H.; Mu, C.; Li, J.; Gao, R.; Zhou, C.; Cao, L.; Liu, J.; Zhu, Y.; Chen, Q.; Wu, S. Hypoxia regulates Hippo signalling through the SIAH2 ubiquitin E3 ligase. Nat. Cell Biol., 2015, 17(1), 95-103.
[http://dx.doi.org/10.1038/ncb3073] [PMID: 25438054]
[34]
Noman, M.Z.; Hasmim, M.; Messai, Y.; Terry, S.; Kieda, C.; Janji, B.; Chouaib, S. Hypoxia: A key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia. Am. J. Physiol. Cell Physiol., 2015, 309(9), C569-C579.
[http://dx.doi.org/10.1152/ajpcell.00207.2015] [PMID: 26310815]
[35]
Multhoff, G.; Vaupel, P. Hypoxia compromises anti-cancer immune responses. Adv Exp Med Biol, 2020, 1232, 131-143.
[http://dx.doi.org/10.1007/978-3-030-34461-0_18] [PMID: 31893404]
[36]
Damgaci, S.; Ibrahim-Hashim, A.; Enriquez-Navas, P.M.; Pilon-Thomas, S.; Guvenis, A.; Gillies, R.J. Hypoxia and acidosis: Immune suppressors and therapeutic targets. Immunology, 2018, 154(3), 354-362.
[http://dx.doi.org/10.1111/imm.12917] [PMID: 29485185]
[37]
Bailey, P.; Chang, D.K.; Nones, K.; Johns, A.L.; Patch, A.M.; Gingras, M.C.; Miller, D.K.; Christ, A.N.; Bruxner, T.J.C.; Quinn, M.C.; Nourse, C.; Murtaugh, L.C.; Harliwong, I.; Idrisoglu, S.; Manning, S.; Nourbakhsh, E.; Wani, S.; Fink, L.; Holmes, O.; Chin, V.; Anderson, M.J.; Kazakoff, S.; Leonard, C.; Newell, F.; Waddell, N.; Wood, S.; Xu, Q.; Wilson, P.J.; Cloonan, N.; Kassahn, K.S.; Taylor, D.; Quek, K.; Robertson, A.; Pantano, L.; Mincarelli, L.; Sanchez, L.N.; Evers, L.; Wu, J.; Pinese, M.; Cowley, M.J.; Jones, M.D.; Colvin, E.K.; Nagrial, A.M.; Humphrey, E.S.; Chantrill, L.A.; Mawson, A.; Humphris, J.; Chou, A.; Pajic, M.; Scarlett, C.J.; Pinho, A.V.; Giry-Laterriere, M.; Rooman, I.; Samra, J.S.; Kench, J.G.; Lovell, J.A.; Merrett, N.D.; Toon, C.W.; Epari, K.; Nguyen, N.Q.; Barbour, A.; Zeps, N.; Moran-Jones, K.; Jamieson, N.B.; Graham, J.S.; Duthie, F.; Oien, K.; Hair, J.; Grützmann, R.; Maitra, A.; Iacobuzio-Donahue, C.A.; Wolfgang, C.L.; Morgan, R.A.; Lawlor, R.T.; Corbo, V.; Bassi, C.; Rusev, B.; Capelli, P.; Salvia, R.; Tortora, G.; Mukhopadhyay, D.; Petersen, G.M.; Munzy, D.M.; Fisher, W.E.; Karim, S.A.; Eshleman, J.R.; Hruban, R.H.; Pilarsky, C.; Morton, J.P.; Sansom, O.J.; Scarpa, A.; Musgrove, E.A.; Bailey, U.M.H.; Hofmann, O.; Sutherland, R.L.; Wheeler, D.A.; Gill, A.J.; Gibbs, R.A.; Pearson, J.V.; Waddell, N.; Biankin, A.V.; Grimmond, S.M. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 2016, 531(7592), 47-52.
[http://dx.doi.org/10.1038/nature16965] [PMID: 26909576]
[38]
Collisson, E.A.; Sadanandam, A.; Olson, P.; Gibb, W.J.; Truitt, M.; Gu, S.; Cooc, J.; Weinkle, J.; Kim, G.E.; Jakkula, L.; Feiler, H.S.; Ko, A.H.; Olshen, A.B.; Danenberg, K.L.; Tempero, M.A.; Spellman, P.T.; Hanahan, D.; Gray, J.W. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med., 2011, 17(4), 500-503.
[http://dx.doi.org/10.1038/nm.2344] [PMID: 21460848]
[39]
Ullmann, P.; Nurmik, M.; Schmitz, M.; Rodriguez, F.; Weiler, J.; Qureshi-Baig, K.; Felten, P.; Nazarov, P.V.; Nicot, N.; Zuegel, N.; Haan, S.; Letellier, E. Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity. Cancer Lett., 2019, 450, 32-41.
[http://dx.doi.org/10.1016/j.canlet.2019.02.030] [PMID: 30790680]
[40]
Gervin, E.; Shin, B.; Opperman, R.; Cullen, M.; Feser, R.; Maiti, S.; Majumder, M. Chemically induced hypoxia enhances miRNA functions in breast cancer. Cancers, 2020, 12(8), 2008.
[http://dx.doi.org/10.3390/cancers12082008] [PMID: 32707933]
[41]
Xu, K.; Zhan, Y.; Yuan, Z.; Qiu, Y.; Wang, H.; Fan, G.; Wang, J.; Li, W.; Cao, Y.; Shen, X.; Zhang, J.; Liang, X.; Yin, P. Hypoxia induces drug resistance in colorectal cancer through the HIF-1α/miR-338-5p/IL-6 feedback loop. Mol. Ther., 2019, 27(10), 1810-1824.
[http://dx.doi.org/10.1016/j.ymthe.2019.05.017] [PMID: 31208913]
[42]
Cao, W.; Zeng, Z.; He, Z.; Lei, S. Hypoxic pancreatic stellate cell-derived exosomal mirnas promote proliferation and invasion of pancreatic cancer through the PTEN/AKT pathway. Aging, 2021, 13(5), 7120-7132.
[http://dx.doi.org/10.18632/aging.202569] [PMID: 33653966]

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