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Current Medicinal Chemistry

Current Medicinal Chemistry

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

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Research Article

LncRNA-associated ceRNA Network Revealing the Potential Regulatory Roles of Ferroptosis and Immune Infiltration in Osteosarcoma as well as Construction of the Prognostic Model

Author(s): Zhixian Lin, Zhen Wang, Danyan Shao, Jiangfeng Chen, Yunxia Liu and Yongwei Yao*

Volume 33, Issue 1, 2026

Published on: 27 December, 2024

Page: [102 - 121] Pages: 20

DOI: 10.2174/0109298673322797241001054036

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Abstract

Background: Osteosarcoma (OS) is the most common primary bone malignancy in the world. Increasing studies indicate that long non-coding RNAs (lncRNAs) are involved in ferroptosis and OS progression. Therefore, this study aims to identify ferroptosis- related lncRNAs (FRlncRNAs), explore potential competing endogenous RNA (ceRNA) networks, and establish a new model for predicting OS prognosis.

Methods: Firstly, we downloaded data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), University of California, Santa Cruz (UCSC), and FerrDB, and screened for differentially expressed FRlncRNAs (DEFRlncRNAs) between OS patients and healthy controls. Then, we constructed the ceRNA network using the Lncbase 3.0, starBase, miRDB, miRTarBase, and TargetScan databases. Subsequently, prognosis- related DEFRlncRNAs were selected through Cox analysis, and a prognostic model was constructed. Next, the proportions of different immune cells in high and low-risk groups were quantified and evaluated using the “CIBERSORT” algorithm. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on prognosis-related DEFRlncRNAs to identify topranked biological processes and pathways.

Results: We identified 247 DEFRlncRNAs and constructed the ceRNA network comprising 37 lncRNAs, 84 microRNAs (miRNAs), and 865 messenger RNAs (mRNAs). Subsequently, we obtained 8 prognosis-related DEFRlncRNAs (AL645728.1, AL161785.1, LINC00539, AL590764.1, OLMALINC, AC110995.1, AC091180.2, and AL160006.1) and constructed a prognostic model, where metastasis and risk score were identified as important clinical factors for predicting OS prognosis. Additionally, only OLMALINC and AL160006.1 had corresponding target miRNAs in the prognosis-related ceRNA network. Lastly, we revealed the infiltration proportions of different immune cells in OS, with higher proportions of macrophages (M0 and M2 subgroups) and T cells (T cells CD4 memory resting and T cells CD8) observed.

Conclusion: This study explored the ferroptosis-related lncRNA-miRNA-mRNA regulatory network in OS, constructed a ferroptosis-related prognostic model, and characterized its association with immune infiltration, providing new insights into the pathological mechanisms and targeted therapy development for OS.

Keywords: Osteosarcoma, ferroptosis, LncRNAs, ceRNA network, immune infiltration, prognosis.

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[1]
Beird, H.C.; Bielack, S.S.; Flanagan, A.M.; Gill, J.; Heymann, D.; Janeway, K.A.; Livingston, J.A.; Roberts, R.D.; Strauss, S.J.; Gorlick, R. Osteosarcoma. Nat. Rev. Dis. Primers, 2022, 8(1), 77.
[http://dx.doi.org/10.1038/s41572-022-00411-4] [PMID: 36481743]
[2]
Mirabello, L.; Troisi, R.J.; Savage, S.A. Osteosarcoma incidence and survival rates from 1973 to 2004. Cancer, 2009, 115(7), 1531-1543.
[http://dx.doi.org/10.1002/cncr.24121] [PMID: 19197972]
[3]
Bishop, M.W.; Janeway, K.A.; Gorlick, R. Future directions in the treatment of osteosarcoma. Curr. Opin. Pediatr., 2016, 28(1), 26-33.
[http://dx.doi.org/10.1097/MOP.0000000000000298] [PMID: 26626558]
[4]
Otoukesh, B.; Boddouhi, B.; Moghtadaei, M.; Kaghazian, P.; Kaghazian, M. Novel molecular insights and new therapeutic strategies in osteosarcoma. Cancer Cell Int., 2018, 18(1), 158.
[http://dx.doi.org/10.1186/s12935-018-0654-4] [PMID: 30349420]
[5]
Beird, H.C.; Bielack, S.S.; Flanagan, A.M.; Gill, J.; Heymann, D.; Janeway, K.A.; Livingston, J.A.; Roberts, R.D.; Strauss, S.J.; Gorlick, R. Osteosarcoma. Nat. Rev. Dis. Primers, 2022, 8, 77.
[http://dx.doi.org/10.1038/s41572-022-00409-y] [PMID: 36481668]
[6]
Gill, J.; Gorlick, R. Advancing therapy for osteosarcoma. Nat. Rev. Clin. Oncol., 2021, 18(10), 609-624.
[http://dx.doi.org/10.1038/s41571-021-00519-8] [PMID: 34131316]
[7]
Lei, T.; Qian, H.; Lei, P.; Hu, Y. Ferroptosis-related gene signature associates with immunity and predicts prognosis accurately in patients with osteosarcoma. Cancer Sci., 2021, 112(11), 4785-4798.
[http://dx.doi.org/10.1111/cas.15131] [PMID: 34506683]
[8]
Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; Morrison, B., III; Stockwell, B.R. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell, 2012, 149(5), 1060-1072.
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[9]
Li, J.; Cao, F.; Yin, H.; Huang, Z.; Lin, Z.; Mao, N.; Sun, B.; Wang, G. Ferroptosis: Past, present and future. Cell Death Dis., 2020, 11(2), 88.
[http://dx.doi.org/10.1038/s41419-020-2298-2] [PMID: 32015325]
[10]
Xie, Y.; Hou, W.; Song, X.; Yu, Y.; Huang, J.; Sun, X.; Kang, R.; Tang, D. Ferroptosis: Process and function. Cell Death Differ., 2016, 23(3), 369-379.
[http://dx.doi.org/10.1038/cdd.2015.158] [PMID: 26794443]
[11]
Cai, S.; Zhang, B.; Huang, C.; Deng, Y.; Wang, C.; Yang, Y.; Xiang, Z.; Ni, Y.; Wang, Z.; Wang, L.; Zhang, B.; Guo, X.; He, J.; Ma, K.; Yu, Z. CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway. Cancer Lett., 2023, 579, 216465.
[http://dx.doi.org/10.1016/j.canlet.2023.216465] [PMID: 38084702]
[12]
Sun, G.; Wang, J.; Liu, F.; Zhao, C.; Cui, S.; Wang, Z.; Liu, Z.; Zhang, Q.; Xiang, C.; Zhang, Y.; Galons, H.; Yu, P.; Teng, Y. G-4 inhibits triple negative breast cancer by inducing cell apoptosis and promoting LCN2-dependent ferroptosis. Biochem. Pharmacol., 2024, 222, 116077.
[http://dx.doi.org/10.1016/j.bcp.2024.116077] [PMID: 38395264]
[13]
Cui, W.; Guo, M.; Liu, D.; Xiao, P.; Yang, C.; Huang, H.; Liang, C.; Yang, Y.; Fu, X.; Zhang, Y.; Liu, J.; Shi, S.; Cong, J.; Han, Z.; Xu, Y.; Du, L.; Yin, C.; Zhang, Y.; Sun, J.; Gu, W.; Chai, R.; Zhu, S.; Chu, B. Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition. Nat. Cell Biol., 2024, 26(1), 124-137.
[http://dx.doi.org/10.1038/s41556-023-01314-6] [PMID: 38168770]
[14]
Isani, G.; Bertocchi, M.; Andreani, G.; Farruggia, G.; Cappadone, C.; Salaroli, R.; Forni, M.; Bernardini, C. Cytotoxic effects of Artemisia annua L. and pure artemisinin on the D-17 canine osteosarcoma cell line. Oxid. Med. Cell. Longev., 2019, 2019, 1-9.
[http://dx.doi.org/10.1155/2019/1615758] [PMID: 31354901]
[15]
Liu, X.; Du, S.; Wang, S.; Ye, K. Ferroptosis in osteosarcoma: A promising future. Front. Oncol., 2022, 12, 1031779.
[http://dx.doi.org/10.3389/fonc.2022.1031779] [PMID: 36457488]
[16]
Wang, W.; Green, M.; Choi, J.E.; Gijón, M.; Kennedy, P.D.; Johnson, J.K.; Liao, P.; Lang, X.; Kryczek, I.; Sell, A.; Xia, H.; Zhou, J.; Li, G.; Li, J.; Li, W.; Wei, S.; Vatan, L.; Zhang, H.; Szeliga, W.; Gu, W.; Liu, R.; Lawrence, T.S.; Lamb, C.; Tanno, Y.; Cieslik, M.; Stone, E.; Georgiou, G.; Chan, T.A.; Chinnaiyan, A.; Zou, W. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature, 2019, 569(7755), 270-274.
[http://dx.doi.org/10.1038/s41586-019-1170-y] [PMID: 31043744]
[17]
Liao, P.; Wang, W.; Wang, W.; Kryczek, I.; Li, X.; Bian, Y.; Sell, A.; Wei, S.; Grove, S.; Johnson, J.K.; Kennedy, P.D.; Gijón, M.; Shah, Y.M.; Zou, W. CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4. Cancer Cell, 2022, 40(4), 365-378.e6.
[http://dx.doi.org/10.1016/j.ccell.2022.02.003] [PMID: 35216678]
[18]
Morris, K.V.; Mattick, J.S. The rise of regulatory RNA. Nat. Rev. Genet., 2014, 15(6), 423-437.
[http://dx.doi.org/10.1038/nrg3722] [PMID: 24776770]
[19]
Wang, W.; Min, L.; Qiu, X.; Wu, X.; Liu, C.; Ma, J.; Zhang, D.; Zhu, L. Biological function of long non-coding RNA (LncRNA) xist. Front. Cell Dev. Biol., 2021, 9, 645647.
[http://dx.doi.org/10.3389/fcell.2021.645647] [PMID: 34178980]
[20]
Schmitt, AM; Chang, HY. Long noncoding RNAs in cancer pathways. Cancer Cell, 2016, 452-463.
[http://dx.doi.org/10.1016/j.ccell.2016.03.010]
[21]
Thomson, D.W.; Dinger, M.E. Endogenous microRNA sponges: Evidence and controversy. Nat. Rev. Genet., 2016, 17(5), 272-283.
[http://dx.doi.org/10.1038/nrg.2016.20] [PMID: 27040487]
[22]
Lin, C.; Miao, J.; He, J.; Feng, W.; Chen, X.; Jiang, X.; Liu, J.; Li, B.; Huang, Q.; Liao, S.; Liu, Y. The regulatory mechanism of LncRNA-mediated ceRNA network in osteosarcoma. Sci. Rep., 2022, 12(1), 8756.
[http://dx.doi.org/10.1038/s41598-022-11371-w] [PMID: 35610231]
[23]
Zhang, G.Z.; Wu, Z.L.; Li, C.Y.; Ren, E.H.; Yuan, W.H.; Deng, Y.J.; Xie, Q.Q. Development of a machine learning-based autophagy-related lncRNA signature to improve prognosis prediction in osteosarcoma patients. Front. Mol. Biosci., 2021, 8, 615084.
[http://dx.doi.org/10.3389/fmolb.2021.615084] [PMID: 34095215]
[24]
Li, J.; Li, Y.; Wu, X.; Li, Y. Identification and validation of potential long non-coding RNA biomarkers in predicting survival of patients with head and neck squamous cell carcinoma. Oncol. Lett., 2019, 17(6), 5642-5652.
[http://dx.doi.org/10.3892/ol.2019.10261] [PMID: 31186787]
[25]
Zhang, Z.; Reinikainen, J.; Adeleke, K.A.; Pieterse, M.E.; Groothuis-Oudshoorn, C.G.M. Time-varying covariates and coefficients in Cox regression models. Ann. Transl. Med., 2018, 6(7), 121.
[http://dx.doi.org/10.21037/atm.2018.02.12] [PMID: 29955581]
[26]
Isakoff, M.S.; Bielack, S.S.; Meltzer, P.; Gorlick, R. Osteosarcoma: Current treatment and a collaborative pathway to success. J. Clin. Oncol., 2015, 33(27), 3029-3035.
[http://dx.doi.org/10.1200/JCO.2014.59.4895] [PMID: 26304877]
[27]
Landuzzi, L.; Manara, M.C.; Lollini, P.L.; Scotlandi, K. Patient derived xenografts for genome-driven therapy of osteosarcoma. Cells, 2021, 10(2), 416.
[http://dx.doi.org/10.3390/cells10020416] [PMID: 33671173]
[28]
Schott, C.; Shah, A.T.; Sweet-Cordero, E.A. Genomic complexity of osteosarcoma and its implication for preclinical and clinical targeted therapies. Adv. Exp. Med. Biol., 2020, 1258, 1-19.
[http://dx.doi.org/10.1007/978-3-030-43085-6_1] [PMID: 32767231]
[29]
Ji, S.; Wang, S.; Zhao, X.; Lv, L. Long noncoding RNA NEAT1 regulates the development of osteosarcoma through sponging miR-34a-5p to mediate HOXA13 expression as a competitive endogenous RNA. Mol. Genet. Genomic Med., 2019, 7(6), e673.
[http://dx.doi.org/10.1002/mgg3.673] [PMID: 31044561]
[30]
Zhang, Y.; Luo, M.; Cui, X.; O’Connell, D.; Yang, Y. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA. Cell Death Differ., 2022, 29(9), 1850-1863.
[http://dx.doi.org/10.1038/s41418-022-00970-9] [PMID: 35338333]
[31]
Li, Y.; Lin, S.; Xie, X.; Zhu, H.; Fan, T.; Wang, S. Highly enriched exosomal lncRNA OIP5-AS1 regulates osteosarcoma tumor angiogenesis and autophagy through miR-153 and ATG5. Am. J. Transl. Res., 2021, 13(5), 4211-4223.
[PMID: 34150009]
[32]
Dai, J.; Xu, L.; Hu, X.; Han, G.; Jiang, H.; Sun, H.; Zhu, G.; Tang, X. Long noncoding RNA OIP5-AS1 accelerates CDK14 expression to promote osteosarcoma tumorigenesis via targeting miR-223. Biomed. Pharmacother., 2018, 106, 1441-1447.
[http://dx.doi.org/10.1016/j.biopha.2018.07.109] [PMID: 30119217]
[33]
Yan, Y.; Liu, X.; Li, Y.; Yan, J.; Zhao, P.; Yang, L. EPB41L4A-AS1 and UNC5B-AS1 have diagnostic and prognostic significance in osteosarcoma. J. Orthop. Surg. Res., 2023, 18(1), 261.
[http://dx.doi.org/10.1186/s13018-023-03754-0] [PMID: 36998043]
[34]
Jin, H.; Wang, H.; Jin, X.; Wang, W. Long non-coding RNA H19 regulates LASP1 expression in osteosarcoma by competitively binding to miR-29a-3p. Oncol. Rep., 2021, 46(3), 207.
[http://dx.doi.org/10.3892/or.2021.8158] [PMID: 34328197]
[35]
Zhang, R.; Pan, T.; Xiang, Y.; Zhang, M.; Xie, H.; Liang, Z.; Chen, B.; Xu, C.; Wang, J.; Huang, X.; Zhu, Q.; Zhao, Z.; Gao, Q.; Wen, C.; Liu, W.; Ma, W.; Feng, J.; Sun, X.; Duan, T.; Lai-Han Leung, E.; Xie, T.; Wu, Q.; Sui, X. Curcumenol triggered ferroptosis in lung cancer cells via lncRNA H19/miR-19b-3p/FTH1 axis. Bioact. Mater., 2022, 13, 23-36.
[http://dx.doi.org/10.1016/j.bioactmat.2021.11.013] [PMID: 35224289]
[36]
Shen, B.; Zhou, N.; Hu, T.; Zhao, W.; Wu, D.; Wang, S. LncRNA MEG3 negatively modified osteosarcoma development through regulation of miR-361-5p and FoxM1. J. Cell. Physiol., 2019, 234(8), 13464-13480.
[http://dx.doi.org/10.1002/jcp.28026] [PMID: 30624782]
[37]
Zhu, C.; Chen, B.; He, X.; Li, W.; Wang, S.; Zhu, X.; Li, Y.; Wan, P.; Li, X. LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis. Mol. Biol. Rep., 2024, 51(1), 139.
[http://dx.doi.org/10.1007/s11033-023-09095-9] [PMID: 38236340]
[38]
Bian, X.; Sun, Y.M.; Wang, L.M.; Shang, Y.L. ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503–5p. Biochem. Biophys. Res. Commun., 2021, 548, 112-119.
[http://dx.doi.org/10.1016/j.bbrc.2021.02.072] [PMID: 33640603]
[39]
Song, J.; Wu, X.; Liu, F.; Li, M.; Sun, Y.; Wang, Y.; Wang, C.; Zhu, K.; Jia, X.; Wang, B.; Ma, X. Long non- coding RNA PVT1 promotes glycolysis and tumor progression by regulating miR-497/HK2 axis in osteosarcoma. Biochem. Biophys. Res. Commun., 2017, 490(2), 217-224.
[http://dx.doi.org/10.1016/j.bbrc.2017.06.024] [PMID: 28602700]
[40]
He, G.N.; Bao, N.R.; Wang, S.; Xi, M.; Zhang, T.H.; Chen, F.S. Ketamine induces ferroptosis of liver cancer cells by targeting lncRNA PVT1/miR-214-3p/GPX4. Drug Des. Devel. Ther., 2021, 15, 3965-3978.
[http://dx.doi.org/10.2147/DDDT.S332847] [PMID: 34566408]
[41]
Fu, D.; Lu, C.; Qu, X.; Li, P.; Chen, K.; Shan, L.; Zhu, X. LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis. Aging, 2019, 11(19), 8374-8385.
[http://dx.doi.org/10.18632/aging.102325] [PMID: 31600142]
[42]
Li, S.; Liu, F.; Pei, Y.; Wang, W.; Zheng, K.; Zhang, X. Long noncoding RNA TTN-AS1 enhances the malignant characteristics of osteosarcoma by acting as a competing endogenous RNA on microRNA-376a thereby upregulating dickkopf-1. Aging, 2019, 11(18), 7678-7693.
[http://dx.doi.org/10.18632/aging.102280] [PMID: 31525734]
[43]
Meng, X.; Zhang, Z.; Chen, L.; Wang, X.; Zhang, Q.; Liu, S. Silencing of the long non-coding RNA TTN-AS1 attenuates the malignant progression of osteosarcoma cells by regulating the miR-16-1-3p/TFAP4 axis. Front. Oncol., 2021, 11, 652835.
[http://dx.doi.org/10.3389/fonc.2021.652835] [PMID: 34141611]
[44]
Huang, S.; Zhu, X.; Ke, Y.; Xiao, D.; Liang, C.; Chen, J.; Chang, Y. LncRNA FTX inhibition restrains osteosarcoma proliferation and migration via modulating miR-320a/TXNRD1. Cancer Biol. Ther., 2020, 21(4), 379-387.
[http://dx.doi.org/10.1080/15384047.2019.1702405] [PMID: 31920141]
[45]
Li, Y.; Ma, Z.; Li, W.; Xu, X.; Shen, P.; Zhang, S.; Cheng, B.; Xia, J. PDPN+ CAFs facilitate the motility of OSCC cells by inhibiting ferroptosis via transferring exosomal lncRNA FTX. Cell Death Dis., 2023, 14(11), 759.
[http://dx.doi.org/10.1038/s41419-023-06280-3] [PMID: 37993428]
[46]
Ma, Q.; Dai, X.; Lu, W.; Qu, X.; Liu, N.; Zhu, C. Silencing long non-coding RNA MEG8 inhibits the proliferation and induces the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Biochem. Biophys. Res. Commun., 2021, 556, 72-78.
[http://dx.doi.org/10.1016/j.bbrc.2021.03.132] [PMID: 33839417]
[47]
Liu, C.W.; Liu, D.; Peng, D. Long non-coding RNA ZFAS1 regulates NOB1 expression through interacting with miR-646 and promotes tumorigenesis in osteosarcoma. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(8), 3206-3216.
[http://dx.doi.org/10.26355/eurrev_201904_17679] [PMID: 31081072]
[48]
Yang, Y.; Tai, W.; Lu, N.; Li, T.; Liu, Y.; Wu, W.; Li, Z.; Pu, L.; Zhao, X.; Zhang, T.; Dong, Z. lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis. Aging, 2020, 12(10), 9085-9102.
[http://dx.doi.org/10.18632/aging.103176] [PMID: 32453709]
[49]
Yu, X.; Jiang, Y.; Hu, X.; Ge, X. LINC00839/miR- 519d-3p/JMJD6 axis modulated cell viability, apoptosis, migration and invasiveness of lung cancer cells. Folia Histochem. Cytobiol., 2021, 59(4), 271-281.
[http://dx.doi.org/10.5603/FHC.a2021.0022] [PMID: 34734406]
[50]
Zhou, X.; Chang, Y.; Zhu, L.; Shen, C.; Qian, J.; Chang, R. LINC00839/miR-144-3p/WTAP (WT1 Associated protein) axis is involved in regulating hepatocellular carcinoma progression. Bioengineered, 2021, 12(2), 10849-10861.
[http://dx.doi.org/10.1080/21655979.2021.1990578] [PMID: 34634995]
[51]
Yang, L.; Pei, L.; Yi, J. LINC00839 regulates proliferation, migration, invasion, apoptosis and glycolysis in neuroblastoma cells through miR-338-3p/GLUT1 axis. Neuropsychiatr. Dis. Treat., 2021, 17, 2027-2040.
[http://dx.doi.org/10.2147/NDT.S309467] [PMID: 34188473]
[52]
Zhang, Q.; Wei, J.; Li, N.; Liu, B. LINC00839 promotes neuroblastoma progression by sponging miR-454-3p to up-regulate NEUROD1. Neurochem. Res., 2022, 47(8), 2278-2293.
[http://dx.doi.org/10.1007/s11064-022-03613-0] [PMID: 35606572]
[53]
Liu, P.; Fu, R.; Chen, K.; Zhang, L.; Wang, S.; Liang, W.; Zou, H.; Tao, L.; Jia, W. ETV5-mediated upregulation of lncRNA CTBP1-DT as a ceRNA facilitates HGSOC progression by regulating miR-188-5p/MAP3K3 axis. Cell Death Dis., 2021, 12(12), 1146.
[http://dx.doi.org/10.1038/s41419-021-04256-9] [PMID: 34887384]
[54]
Yu, J.; Wang, F.; Zhang, J.; Li, J.; Chen, X.; Han, G. LINC00667/miR-449b-5p/YY1 axis promotes cell proliferation and migration in colorectal cancer. Cancer Cell Int., 2020, 20(1), 322.
[http://dx.doi.org/10.1186/s12935-020-01377-7] [PMID: 32694944]
[55]
Pan, J.; Zang, Y. LINC00667 promotes progression of esophageal cancer cells by regulating miR-200b-3p/SLC2A3 axis. Dig. Dis. Sci., 2022, 67(7), 2936-2947.
[http://dx.doi.org/10.1007/s10620-021-07145-5] [PMID: 34313922]
[56]
Liao, B.; Yi, Y.; Zeng, L.; Wang, Z.; Zhu, X.; Liu, J.; Xie, B.; Liu, Y. LINC00667 sponges miR-4319 to promote the development of nasopharyngeal carcinoma by increasing FOXQ1 expression. Front. Oncol., 2021, 10, 632813.
[http://dx.doi.org/10.3389/fonc.2020.632813] [PMID: 33569351]
[57]
Yang, Y.; Li, S.; Cao, J.; Li, Y.; Hu, H.; Wu, Z. RRM2 regulated By LINC00667/miR-143-3p signal is responsible for non-small cell lung cancer cell progression. OncoTargets Ther., 2019, 12, 9927-9939.
[http://dx.doi.org/10.2147/OTT.S221339] [PMID: 31819489]
[58]
Long, X.; Li, Q.; Zhi, L.J.; Li, J.M.; Wang, Z.Y. LINC00205 modulates the expression of EPHX1 through the inhibition of miR-184 in hepatocellular carcinoma as a ceRNA. J. Cell. Physiol., 2020, 235(3), 3013-3021.
[http://dx.doi.org/10.1002/jcp.29206] [PMID: 31566711]
[59]
Cheng, T.; Yao, Y.; Zhang, S.; Zhang, X.N.; Zhang, A.H.; Yang, W. LINC00205, a YY1-modulated lncRNA, serves as a sponge for miR-26a-5p facilitating the proliferation of hepatocellular carcinoma cells by elevating CDK6. Eur. Rev. Med. Pharmacol. Sci., 2021, 25, 6208-6219.
[http://dx.doi.org/10.26355/eurrev_202110_26991]
[60]
Xie, H.; Shi, S.; Chen, Q.; Chen, Z. LncRNA TRG-AS1 promotes glioblastoma cell proliferation by competitively binding with miR-877-5p to regulate SUZ12 expression. Pathol. Res. Pract., 2019, 215(8), 152476.
[http://dx.doi.org/10.1016/j.prp.2019.152476] [PMID: 31196742]
[61]
Zhu, J.; Dai, H.; Li, X.; Guo, L.; Sun, X.; Zheng, Z.; Xu, C. LncRNA TRG-AS1 inhibits bone metastasis of breast cancer by the miR-877–5p/WISP2 axis. Pathol. Res. Pract., 2023, 243, 154360.
[http://dx.doi.org/10.1016/j.prp.2023.154360] [PMID: 36801505]
[62]
Shi, L.; Luo, B.; Deng, L.; Zhang, Q.; Li, Y.; Sun, D.; Zhang, H.; Zhuang, L. The lncRNA TRG-AS1 promotes the growth of colorectal cancer cells through the regulation of P2RY10/GNA13. Scand. J. Gastroenterol., 2024, 59(6), 710-721.
[http://dx.doi.org/10.1080/00365521.2024.2318363] [PMID: 38357893]
[63]
Zhang, M.; Zhu, W.; Haeryfar, M.; Jiang, S.; Jiang, X.; Chen, W.; Li, J. Long non-coding RNA TRG-AS1 promoted proliferation and invasion of lung cancer cells through the miR-224-5p/SMAD4 axis. OncoTargets Ther., 2021, 14, 4415-4426.
[http://dx.doi.org/10.2147/OTT.S297336] [PMID: 34408438]
[64]
Chen, Q.; Xie, J.; Yang, Y. Long non-coding RNA NRSN2-AS1 facilitates tumorigenesis and progression of ovarian cancer via miR-744-5p/PRKX axis. Biol. Reprod., 2022, 106(3), 526-539.
[http://dx.doi.org/10.1093/biolre/ioab212] [PMID: 34791059]
[65]
Liu, Z.; Wang, J.; Tong, H.; Wang, X.; Zhang, D.; Fan, Q. LINC00668 modulates SOCS5 expression through competitively sponging miR-518c-3p to facilitate glioma cell proliferation. Neurochem. Res., 2020, 45(7), 1614-1625.
[http://dx.doi.org/10.1007/s11064-020-02988-2] [PMID: 32279214]
[66]
Xuan, W.; Zhou, C.; You, G. LncRNA LINC00668 promotes cell proliferation, migration, invasion ability and EMT process in hepatocellular carcinoma by targeting miR-532-5p/YY1 axis. Biosci. Rep., 2020, 40(5), BSR20192697.
[http://dx.doi.org/10.1042/BSR20192697] [PMID: 32249890]
[67]
Lu, Z.; Xiao, Z.; Wang, Q.; Pan, C.; Xia, Y.; Wu, W.; Chen, L. LINC00668 promoted non-small lung cancer progression by miR-518c-3p/TRIP4 axis. Cancer Biomark., 2023, 38(3), 379-391.
[http://dx.doi.org/10.3233/CBM-230154] [PMID: 37718780]
[68]
Li, M.; Wang, Q.; Xue, F.; Wu, Y. lncRNA- CYTOR works as an oncogene through the CYTOR /miR-3679-5p/ MACC1 axis in colorectal cancer. DNA Cell Biol., 2019, 38(6), 572-582.
[http://dx.doi.org/10.1089/dna.2018.4548] [PMID: 31144988]
[69]
Hu, B.; Yang, X.B.; Yang, X.; Sang, X.T. LncRNA CYTOR affects the proliferation, cell cycle and apoptosis of hepatocellular carcinoma cells by regulating the miR-125b-5p/KIAA1522 axis. Aging, 2021, 13(2), 2626-2639.
[http://dx.doi.org/10.18632/aging.202306] [PMID: 33318318]
[70]
Wang, D.; Zhu, X.; Siqin, B.; Ren, C.; Yi, F. Long non- coding RNA CYTOR modulates cancer progression through miR-136-5p/MAT2B axis in renal cell carcinoma. Toxicol. Appl. Pharmacol., 2022, 447, 116067.
[http://dx.doi.org/10.1016/j.taap.2022.116067] [PMID: 35597301]
[71]
Dong, X.; Yang, Z.; Yang, H.; Li, D.; Qiu, X. Long non- coding RNA MIR4435-2HG promotes colorectal cancer proliferation and metastasis through miR-206/YAP1 axis. Front. Oncol., 2020, 10, 160.
[http://dx.doi.org/10.3389/fonc.2020.00160] [PMID: 32154166]
[72]
Gao, L.F.; Li, W.; Liu, Y.G.; Zhang, C.; Gao, W.N.; Wang, L. Inhibition of MIR4435-2HG on invasion, migration, and EMT of gastric carcinoma cells by mediating MiR-138-5p/Sox4 axis. Front. Oncol., 2021, 11, 661288.
[http://dx.doi.org/10.3389/fonc.2021.661288] [PMID: 34532282]
[73]
Shen, W.; Zhang, J.; Pan, Y.; Jin, Y. LncRNA MIR4435-2HG functions as a ceRNA against miR-125a-5p and promotes neuroglioma development by upregulating TAZ. J. Clin. Lab. Anal., 2021, 35(12), e24066.
[http://dx.doi.org/10.1002/jcla.24066] [PMID: 34714963]
[74]
Ma, D.M.; Sun, D.; Wang, J.; Jin, D.H.; Li, Y.; Han, Y.E. Long non-coding RNA MIR4435-2HG recruits miR-802 from FLOT2 to promote melanoma progression. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(5), 2616-2624.
[http://dx.doi.org/10.26355/eurrev_202003_20530] [PMID: 32196611]
[75]
Zhao, Y.; Zhang, X.; Wang, J.; Li, Y.; Wu, Y.; Liu, J. Long non-coding RNA ZSCAN16-AS1 promotes the malignant progression of melanoma through regulating the miR-503-5p/ARL2 axis. Clin. Cosmet. Investig. Dermatol., 2023, 16, 1821-1831.
[http://dx.doi.org/10.2147/CCID.S407323] [PMID: 37483470]
[76]
Lv, C.; Wan, Q.; Shen, C.; Wu, H.; Zhou, B.; Wang, W. Long non-coding RNA ZSCAN16-AS1 promotes the malignant properties of hepatocellular carcinoma by decoying microRNA-451a and consequently increasing ATF2 expression. Mol. Med. Rep., 2021, 24(5), 780.
[http://dx.doi.org/10.3892/mmr.2021.12420] [PMID: 34498716]
[77]
Zhang, R.; Li, J.; Badescu, D.; Karaplis, A.; Ragoussis, J.; Kremer, R. PTHrP regulates fatty acid metabolism via novel lncRNA in breast cancer initiation and progression models. Cancers, 2023, 15(15), 3763.
[http://dx.doi.org/10.3390/cancers15153763] [PMID: 37568579]
[78]
Liao, T.; Lu, Y.; Li, W.; Wang, K.; Zhang, Y.; Luo, Z.; Ju, Y.; Ouyang, M. Construction and validation of a glycolysis-related lncRNA signature for prognosis prediction in stomach adenocarcinoma. Front. Genet., 2022, 13, 794621.
[http://dx.doi.org/10.3389/fgene.2022.794621] [PMID: 36313430]
[79]
Gong, Z.; Li, Q.; Li, J.; Xie, J.; Wang, W. A novel signature based on autophagy-related lncRNA for prognostic prediction and candidate drugs for lung adenocarcinoma. Transl. Cancer Res., 2022, 11(1), 14-28.
[http://dx.doi.org/10.21037/tcr-21-1554] [PMID: 35261881]
[80]
Zeng, J.; Li, M.; Dai, K.; Zuo, B.; Guo, J.; Zang, L. A novel glycolysis-related long noncoding RNA signature for predicting overall survival in gastric cancer. Pathol. Oncol. Res., 2022, 28, 1610643.
[http://dx.doi.org/10.3389/pore.2022.1610643] [PMID: 36419649]
[81]
Ni, S.; Hong, J.; Li, W.; Ye, M.; Li, J. Construction of a cuproptosis-related LNCRNA signature for predicting prognosis and immune landscape in osteosarcoma patients. Cancer Med., 2023, 12(4), 5009-5024.
[http://dx.doi.org/10.1002/cam4.5214] [PMID: 36129020]
[82]
Ren, Y.; Da, J.; Ren, J.; Song, Y.; Han, J. An autophagy-related long non-coding RNA signature in tongue squamous cell carcinoma. BMC Oral Health, 2023, 23(1), 120.
[http://dx.doi.org/10.1186/s12903-023-02806-5] [PMID: 36814212]
[83]
Lin, Z.; Wu, Z.; Luo, W. Bulk and single-cell sequencing identified a prognostic model based on the macrophage and lipid metabolism related signatures for osteosarcoma patients. Heliyon, 2024, 10(4), e26091.
[http://dx.doi.org/10.1016/j.heliyon.2024.e26091] [PMID: 38404899]
[84]
Feng, J.; Wang, J.; Xu, Y.; Lu, F.; Zhang, J.; Han, X.; Zhang, C.; Wang, G. Construction and validation of a novel cuproptosis-mitochondrion prognostic model related with tumor immunity in osteosarcoma. PLoS One, 2023, 18(7), e0288180.
[http://dx.doi.org/10.1371/journal.pone.0288180] [PMID: 37405988]
[85]
Chen, Y.; Yan, W.; Wang, H.; Ou, Z.; Chen, H.; Huang, Z.; Yang, J.; Liu, B.; Ou, F.; Zhang, H. The prognostic model established by the differential expression genes based on CD8+ T cells to evaluate the prognosis and the response to immunotherapy in osteosarcoma. Mediators Inflamm., 2023, 2023, 1-11.
[http://dx.doi.org/10.1155/2023/6563609] [PMID: 36816742]
[86]
Ning, B.; Liu, Y.; Xu, T.; Li, Y.; Wei, D.; Huang, T.; Wei, Y. Construction and validation of a prognostic model for osteosarcoma patients based on autophagy-related genes. Discov. Oncol., 2022, 13(1), 146.
[http://dx.doi.org/10.1007/s12672-022-00608-9] [PMID: 36586072]
[87]
Zhang, Z.; Zhang, J.; Duan, Y.; Li, X.; Pan, J.; Wang, G.; Shen, B. Identification of B cell marker genes based on single-cell sequencing to establish a prognostic model and identify immune infiltration in osteosarcoma. Front. Immunol., 2022, 13, 1026701.
[http://dx.doi.org/10.3389/fimmu.2022.1026701] [PMID: 36569871]
[88]
Tong, Y.; Zhang, X.; Zhou, Y. Integrated analysis of multi-omics data to establish a hypoxia-related prognostic model in osteosarcoma. Evol. Bioinform. Online, 2022, 18, 11769343221128537.
[http://dx.doi.org/10.1177/11769343221128537] [PMID: 36325183]
[89]
Yang, J.; Zhang, J.; Na, S.; Wang, Z.; Li, H.; Su, Y.; Ji, L.; Tang, X.; Yang, J.; Xu, L. Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma. Front. Immunol., 2022, 13, 994034.
[http://dx.doi.org/10.3389/fimmu.2022.994034] [PMID: 36225939]
[90]
Chen, W.; Lin, Y.; Huang, J.; Yan, Z.; Cao, H. A novel risk score model based on glycolysis-related genes and a prognostic model for predicting overall survival of osteosarcoma patients. J. Orthop. Res., 2022, 40(10), 2372-2381.
[http://dx.doi.org/10.1002/jor.25259] [PMID: 34997639]
[91]
Huang, H.; Ye, Z.; Li, Z.; Wang, B.; Li, K.; Zhou, K.; Cao, H.; Zheng, J.; Wang, G. Employing machine learning using ferroptosis-related genes to construct a prognosis model for patients with osteosarcoma. Front. Genet., 2023, 14, 1099272.
[http://dx.doi.org/10.3389/fgene.2023.1099272] [PMID: 36733341]
[92]
Li, J.; Wu, F.; Xiao, X.; Su, L.; Guo, X.; Yao, J.; Zhu, H. A novel ferroptosis-related gene signature to predict overall survival in patients with osteosarcoma. Am. J. Transl. Res., 2022, 14(9), 6082-6094.
[PMID: 36247280]
[93]
Zheng, D.; Xia, K.; Wei, Z.; Wei, Z.; Guo, W. Identification of a novel gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment in osteosarcoma. Front. Genet., 2022, 13, 944978.
[http://dx.doi.org/10.3389/fgene.2022.944978] [PMID: 36330451]
[94]
Li, G.; Lei, J.; Xu, D.; Yu, W.; Bai, J.; Wu, G. Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms. Sci. Rep., 2023, 13(1), 5770.
[http://dx.doi.org/10.1038/s41598-023-33009-1] [PMID: 37031292]
[95]
Lang, X.; Green, M.D.; Wang, W.; Yu, J.; Choi, J.E.; Jiang, L.; Liao, P.; Zhou, J.; Zhang, Q.; Dow, A.; Saripalli, A.L.; Kryczek, I.; Wei, S.; Szeliga, W.; Vatan, L.; Stone, E.M.; Georgiou, G.; Cieslik, M.; Wahl, D.R.; Morgan, M.A.; Chinnaiyan, A.M.; Lawrence, T.S.; Zou, W. Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11. Cancer Discov., 2019, 9(12), 1673-1685.
[http://dx.doi.org/10.1158/2159-8290.CD-19-0338] [PMID: 31554642]
[96]
Zeitoun, G.; Sissy, C.E.; Kirilovsky, A.; Anitei, G.; Todosi, A.M.; Marliot, F.; Haicheur, N.; Lagorce, C.; Berger, A.; Zinzindohoué, F.; Galon, J.; Scripcariu, V.; Pagès, F. The immunoscore in the clinical practice of patients with colon and rectal cancers. Chirurgia, 2019, 114(2), 152-161.
[http://dx.doi.org/10.21614/chirurgia.114.2.152] [PMID: 31060646]
[97]
Fridman, W.H.; Pagès, F.; Sautès-Fridman, C.; Galon, J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer, 2012, 12(4), 298-306.
[http://dx.doi.org/10.1038/nrc3245] [PMID: 22419253]
[98]
Sakaguchi, S.; Mikami, N.; Wing, J.B.; Tanaka, A.; Ichiyama, K.; Ohkura, N. Regulatory T cells and human disease. Annu. Rev. Immunol., 2020, 38(1), 541-566.
[http://dx.doi.org/10.1146/annurev-immunol-042718-041717] [PMID: 32017635]
[99]
Campbell, C.; Rudensky, A. Roles of regulatory T cells in tissue pathophysiology and metabolism. Cell Metab., 2020, 31(1), 18-25.
[http://dx.doi.org/10.1016/j.cmet.2019.09.010] [PMID: 31607562]
[100]
Cuadrado, E.; van den Biggelaar, M.; de Kivit, S.; Chen, Y.; Slot, M.; Doubal, I.; Meijer, A.; van Lier, R.A.W.; Borst, J.; Amsen, D. Proteomic analyses of human regulatory T cells reveal adaptations in signaling pathways that protect cellular identity. Immunity, 2018, 48(5), 1046-1059.e6.
[http://dx.doi.org/10.1016/j.immuni.2018.04.008] [PMID: 29752063]
[101]
Duan, M.; Hibbs, M.L.; Chen, W. The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis. Immunol. Cell Biol., 2017, 95(3), 225-235.
[http://dx.doi.org/10.1038/icb.2016.97] [PMID: 27670791]
[102]
Byrne, A.J.; Maher, T.M.; Lloyd, C.M. Pulmonary macrophages: A new therapeutic pathway in fibrosing lung disease? Trends Mol. Med., 2016, 22(4), 303-316.
[http://dx.doi.org/10.1016/j.molmed.2016.02.004] [PMID: 26979628]
[103]
Shapouri-Moghaddam, A.; Mohammadian, S.; Vazini, H.; Taghadosi, M.; Esmaeili, S.A.; Mardani, F.; Seifi, B.; Mohammadi, A.; Afshari, J.T.; Sahebkar, A. Macrophage plasticity, polarization, and function in health and disease. J. Cell. Physiol., 2018, 233(9), 6425-6440.
[http://dx.doi.org/10.1002/jcp.26429] [PMID: 29319160]
[104]
Patel, U.; Rajasingh, S.; Samanta, S.; Cao, T.; Dawn, B.; Rajasingh, J. Macrophage polarization in response to epigenetic modifiers during infection and inflammation. Drug Discov. Today, 2017, 22(1), 186-193.
[http://dx.doi.org/10.1016/j.drudis.2016.08.006] [PMID: 27554801]
[105]
Martinez, F.O.; Sica, A.; Mantovani, A.; Locati, M. Macrophage activation and polarization. Front. Biosci., 2008, 13(13), 453-461.
[http://dx.doi.org/10.2741/2692] [PMID: 17981560]
[106]
Ge, R.; Huang, G.M. Targeting transforming growth factor beta signaling in metastatic osteosarcoma. J. Bone Oncol., 2023, 43, 100513.
[http://dx.doi.org/10.1016/j.jbo.2023.100513] [PMID: 38021074]
[107]
Zheng, C.; Tang, F.; Min, L.; Hornicek, F.; Duan, Z.; Tu, C. PTEN in osteosarcoma: Recent advances and the therapeutic potential. Biochim. Biophys. Acta Rev. Cancer, 2020, 1874(2), 188405.
[http://dx.doi.org/10.1016/j.bbcan.2020.188405] [PMID: 32827577]
[108]
Zhang, J.; Yu, X.H.; Yan, Y.G.; Wang, C.; Wang, W.J. PI3K/Akt signaling in osteosarcoma. Clin. Chim. Acta, 2015, 444, 182-192.
[http://dx.doi.org/10.1016/j.cca.2014.12.041] [PMID: 25704303]
[109]
Yi, J.; Zhu, J.; Wu, J.; Thompson, C.B.; Jiang, X. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc. Natl. Acad. Sci. USA, 2020, 117(49), 31189-31197.
[http://dx.doi.org/10.1073/pnas.2017152117] [PMID: 33229547]
[110]
Walia, M.K.; Ho, P.M.W.; Taylor, S.; Ng, A.J.M.; Gupte, A.; Chalk, A.M.; Zannettino, A.C.W.; Martin, T.J.; Walkley, C.R. Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance. eLife, 2016, 5, e13446.
[http://dx.doi.org/10.7554/eLife.13446] [PMID: 27070462]
[111]
Collins, S.E.; Wiegand, M.E.; Werner, A.N.; Brown, I.N.; Mundo, M.I.; Swango, D.J.; Mouneimne, G.; Charest, P.G. Ras-mediated activation of mTORC2 promotes breast epithelial cell migration and invasion. Mol. Biol. Cell, 2023, 34(2), ar9.
[http://dx.doi.org/10.1091/mbc.E22-06-0236] [PMID: 36542482]
[112]
Beunk, L.; Brown, K.; Nagtegaal, I.; Friedl, P.; Wolf, K. Cancer invasion into musculature: Mechanics, molecules and implications. Semin. Cell Dev. Biol., 2019, 93, 36-45.
[http://dx.doi.org/10.1016/j.semcdb.2018.07.014] [PMID: 30009945]
[113]
Neschadim, A.; Summerlee, A.J.S.; Silvertown, J.D. Targeting the relaxin hormonal pathway in prostate cancer. Int. J. Cancer, 2015, 137(10), 2287-2295.
[http://dx.doi.org/10.1002/ijc.29079] [PMID: 25043063]
[114]
Xu, M.; Hu, X.; Xiao, Z.; Zhang, S.; Lu, Z. Silencing KPNA2 promotes ferroptosis in laryngeal cancer by activating the FoxO signaling pathway. Biochem. Genet., 2024, 20
[http://dx.doi.org/10.1007/s10528-023-10655-8] [PMID: 38379037]

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