Generic placeholder image

Current Cancer Drug Targets

Author(s): Daxiang Liu, Wenjing Wang, Yanzhao Wu, Yongle Qiu and Lan Zhang*

DOI: 10.2174/0115680096258716231026063704

DownloadDownload PDF Flyer Cite As
LINC00887 Acts as an Enhancer RNA to Promote Medullary Thyroid Carcinoma Progression by Binding with FOXQ1

Page: [519 - 533] Pages: 15

  • * (Excluding Mailing and Handling)

Abstract

Background: Medullary thyroid carcinoma (MTC) is a rare but aggressive endocrine malignancy that originates from the parafollicular C cells of the thyroid gland. Enhancer RNAs (eRNAs) are non-coding RNAs transcribed from enhancer regions, which are critical regulators of tumorigenesis. However, the roles and regulatory mechanisms of eRNAs in MTC remain poorly understood. This study aims to identify key eRNAs regulating the malignant phenotype of MTC and to uncover transcription factors involved in the regulation of key eRNAs.

Methods: GSE32662 and GSE114068 were used for the identification of differentially expressed genes, eRNAs, enhancers and enhancer-regulated genes in MTC. Metascape and the transcription factor affinity prediction method were used for gene function enrichment and transcription factor prediction, respectively. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to assess the binding of histone H3 lysine 27 acetylation (H3K27ac)-enriched regions to anti- H3K27ac. RIP-qPCR was used to detect the binding between FOXQ1 and LINC00887. CCK8 and Transwell were performed to measure the proliferation and invasion of MTC cells, respectively. Intracellular reactive oxygen species (ROS) levels were quantified using a ROS assay kit.

Results: Four eRNAs (H1FX-AS1, LINC00887, MCM3AP-AS1 and A1BG-AS1) were screened, among which LINC00887 was the key eRNA promoting the proliferation and invasion of MTC cells. A total of 135 genes controlled by LINC00887-regulated enhancers were identified; among them, BCL2, PRDX1, SFTPD, TPO, GSS, RAD52, ZNF580, and ZFP36L1 were significantly enriched in the “ROS metabolic process” term. As a transcription factor regulating genes enriched in the “ROS metabolic process” term, FOXQ1 could recruit LINC00887. Overexpression of FOXQ1 restored LINC00887 knockdown-induced downregulation of GSS and ZFP36L1 transcription in MTC cells. Additionally, FOXQ1 overexpression counteracted the inhibitory effects of LINC00887 knockdown on the proliferation and invasion of MTC cells and the promotion of intracellular ROS accumulation induced by LINC00887 knockdown.

Conclusion: LINC00887 was identified as a key eRNA promoting the malignant phenotype of MTC cells. The involvement of FOXQ1 was essential for LINC00887 to play a pro-tumorigenic role in MTC. Our findings suggest that the FOXQ1/LINC00887 axis is a potential therapeutic target for MTC.

Graphical Abstract

[1]
Romei, C.; Elisei, R. A narrative review of genetic alterations in primary thyroid epithelial cancer. Int. J. Mol. Sci., 2021, 22(4), 1726.
[http://dx.doi.org/10.3390/ijms22041726] [PMID: 33572167]
[2]
Fagin, J.A.; Wells, S.A., Jr Biologic and clinical perspectives on thyroid cancer. N. Engl. J. Med., 2016, 375(11), 1054-1067.
[http://dx.doi.org/10.1056/NEJMra1501993] [PMID: 27626519]
[3]
Kaliszewski, K.; Ludwig, M.; Ludwig, B.; Mikuła, A.; Greniuk, M.; Rudnicki, J. Update on the diagnosis and management of medullary thyroid cancer: What has changed in recent years? Cancers (Basel), 2022, 14(15), 3643.
[http://dx.doi.org/10.3390/cancers14153643] [PMID: 35892901]
[4]
Kim, M.; Kim, B.H. Current guidelines for management of medullary thyroid carcinoma. Endocrinol. Metab. (Seoul), 2021, 36(3), 514-524.
[http://dx.doi.org/10.3803/EnM.2021.1082] [PMID: 34154310]
[5]
Jaber, T.; Dadu, R.; Hu, M.I. Medullary thyroid carcinoma. Curr. Opin. Endocrinol. Diabetes Obes., 2021, 28(5), 540-546.
[http://dx.doi.org/10.1097/MED.0000000000000662] [PMID: 34292174]
[6]
Bartz-Kurycki, M.A.; Oluwo, O.E.; Morris-Wiseman, L.F. Medullary thyroid carcinoma: recent advances in identification, treatment, and prognosis. Ther. Adv. Endocrinol. Metab., 2021, 12(12), 20420188211049611.
[http://dx.doi.org/10.1177/20420188211049611] [PMID: 34659736]
[7]
Moses, L.E.; Oliver, J.R.; Rotsides, J.M.; Shao, Q.; Patel, K.N.; Morris, L.G.T.; Givi, B. Nodal disease burden and outcome of medullary thyroid carcinoma. Head Neck, 2021, 43(2), 577-584.
[http://dx.doi.org/10.1002/hed.26511] [PMID: 33107153]
[8]
Zhu, W.; Hai, T.; Ye, L.; Cote, G.J. Medullary thyroid carcinoma cell lines contain a self-renewing CD133+ population that is dependent on ret proto-oncogene activity. J. Clin. Endocrinol. Metab., 2010, 95(1), 439-444.
[http://dx.doi.org/10.1210/jc.2009-1485] [PMID: 19897677]
[9]
Stamatakos, M.; Paraskeva, P.; Stefanaki, C.; Katsaronis, P.; Lazaris, A.; Safioleas, K.; Kontzoglou, K. Medullary thyroid carcinoma: The third most common thyroid cancer reviewed. Oncol. Lett., 2011, 2(1), 49-53.
[http://dx.doi.org/10.3892/ol.2010.223] [PMID: 22870127]
[10]
Kukulska, A.; Krajewska, J.; Kolosza, Z.; Paliczka-Cieslik, E.; Kropinska, A.; Pawlaczek, A.; Puch, Z.; Ficek, K.; Lisik, T.; Sygula, D.; Wygoda, Z.; Roskosz, J.; Wydmanski, J.; Jarzab, B. The role of postoperative adjuvant radiotherapy in local recurrence risk in medullary thyroid carcinoma. Endocr. Connect., 2020, 9(1), 1-8.
[http://dx.doi.org/10.1530/EC-19-0387] [PMID: 31778360]
[11]
Ceolin, L.; Duval, M.A.S.; Benini, A.F.; Ferreira, C.V.; Maia, A.L. Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives. Endocr. Relat. Cancer, 2019, 26(9), R499-R518.
[http://dx.doi.org/10.1530/ERC-18-0574] [PMID: 31252403]
[12]
Thomas, C.M.; Asa, S.L.; Ezzat, S.; Sawka, A.M.; Goldstein, D. Diagnosis and pathologic characteristics of medullary thyroid carcinoma-review of current guidelines. Curr. Oncol., 2019, 26(5), 338-344.
[http://dx.doi.org/10.3747/co.26.5539] [PMID: 31708652]
[13]
Contarino, A.; Dolci, A.; Maggioni, M.; Porta, F.M.; Lopez, G.; Verga, U.; Elli, F.M.; Iofrida, E.F.; Cantoni, G.; Mantovani, G.; Arosio, M. Is encapsulated medullary thyroid carcinoma associated with a better prognosis? A case series and a review of the literature. Front. Endocrinol. (Lausanne), 2022, 13, 866572.
[http://dx.doi.org/10.3389/fendo.2022.866572] [PMID: 35574005]
[14]
Cabanillas, M.E.; McFadden, D.G.; Durante, C. Thyroid cancer. Lancet, 2016, 388(10061), 2783-2795.
[http://dx.doi.org/10.1016/S0140-6736(16)30172-6] [PMID: 27240885]
[15]
Rickels, R.; Shilatifard, A. Enhancer logic and mechanics in development and disease. Trends Cell Biol., 2018, 28(8), 608-630.
[http://dx.doi.org/10.1016/j.tcb.2018.04.003] [PMID: 29759817]
[16]
Shlyueva, D.; Stampfel, G.; Stark, A. Transcriptional enhancers: from properties to genome-wide predictions. Nat. Rev. Genet., 2014, 15(4), 272-286.
[http://dx.doi.org/10.1038/nrg3682] [PMID: 24614317]
[17]
Long, H.K.; Prescott, S.L.; Wysocka, J. Ever-changing landscapes: Transcriptional enhancers in development and evolution. Cell, 2016, 167(5), 1170-1187.
[http://dx.doi.org/10.1016/j.cell.2016.09.018] [PMID: 27863239]
[18]
Field, A.; Adelman, K. Evaluating enhancer function and transcription. Annu. Rev. Biochem., 2020, 89(1), 213-234.
[http://dx.doi.org/10.1146/annurev-biochem-011420-095916] [PMID: 32197056]
[19]
Lee, J.H.; Xiong, F.; Li, W. Enhancer RNAs in cancer: regulation, mechanisms and therapeutic potential. RNA Biol., 2020, 17(11), 1550-1559.
[http://dx.doi.org/10.1080/15476286.2020.1712895] [PMID: 31916476]
[20]
Durbin, A.D.; Wang, T.; Wimalasena, V.K.; Zimmerman, M.W.; Li, D.; Dharia, N.V.; Mariani, L.; Shendy, N.A.M.; Nance, S.; Patel, A.G.; Shao, Y.; Mundada, M.; Maxham, L.; Park, P.M.C.; Sigua, L.H.; Morita, K.; Conway, A.S.; Robichaud, A.L.; Perez-Atayde, A.R.; Bikowitz, M.J.; Quinn, T.R.; Wiest, O.; Easton, J.; Schönbrunn, E.; Bulyk, M.L.; Abraham, B.J.; Stegmaier, K.; Look, A.T.; Qi, J. EP300 selectively controls the enhancer landscape of MYCN -amplified neuroblastoma. Cancer Discov., 2022, 12(3), 730-751.
[http://dx.doi.org/10.1158/2159-8290.CD-21-0385] [PMID: 34772733]
[21]
Wang, Q.; Ozer, H.G.; Wang, B.; Zhang, M.; Urabe, G.; Huang, Y.; Kent, K.C.; Guo, L.W. A hierarchical and collaborative BRD4/CEBPD partnership governs vascular smooth muscle cell inflammation. Mol. Ther. Methods Clin. Dev., 2021, 21, 54-66.
[http://dx.doi.org/10.1016/j.omtm.2021.02.021] [PMID: 33768129]
[22]
Creyghton, M.P.; Cheng, A.W.; Welstead, G.G.; Kooistra, T.; Carey, B.W.; Steine, E.J.; Hanna, J.; Lodato, M.A.; Frampton, G.M.; Sharp, P.A.; Boyer, L.A.; Young, R.A.; Jaenisch, R. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. USA, 2010, 107(50), 21931-21936.
[http://dx.doi.org/10.1073/pnas.1016071107] [PMID: 21106759]
[23]
Ye, R.; Cao, C.; Xue, Y. Enhancer RNA: biogenesis, function, and regulation. Essays Biochem., 2020, 64(6), 883-894.
[http://dx.doi.org/10.1042/EBC20200014] [PMID: 33034351]
[24]
Arnold, M.; Stengel, K.R. Emerging insights into enhancer biology and function. Transcription, 2023, 14(1-2), 68-87.
[http://dx.doi.org/10.1080/21541264.2023.2222032] [PMID: 37312570]
[25]
Sengupta, D.; Kannan, A.; Kern, M.; Moreno, M.A.; Vural, E.; Stack, B., Jr; Suen, J.Y.; Tackett, A.J.; Gao, L. Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma. Epigenetics, 2015, 10(6), 460-466.
[http://dx.doi.org/10.1080/15592294.2015.1034416] [PMID: 25941994]
[26]
Nagarajan, S.; Hossan, T.; Alawi, M.; Najafova, Z.; Indenbirken, D.; Bedi, U.; Taipaleenmäki, H.; Ben-Batalla, I.; Scheller, M.; Loges, S.; Knapp, S.; Hesse, E.; Chiang, C.M.; Grundhoff, A.; Johnsen, S.A. Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription. Cell Rep., 2014, 8(2), 460-469.
[http://dx.doi.org/10.1016/j.celrep.2014.06.016] [PMID: 25017071]
[27]
Zhang, Z.; Lee, J.H.; Ruan, H.; Ye, Y.; Krakowiak, J.; Hu, Q.; Xiang, Y.; Gong, J.; Zhou, B.; Wang, L.; Lin, C.; Diao, L.; Mills, G.B.; Li, W.; Han, L. Transcriptional landscape and clinical utility of enhancer RNAs for eRNA-targeted therapy in cancer. Nat. Commun., 2019, 10(1), 4562.
[http://dx.doi.org/10.1038/s41467-019-12543-5] [PMID: 31594934]
[28]
Adhikary, S.; Roy, S.; Chacon, J.; Gadad, S.S.; Das, C. Implications of Enhancer Transcription and eRNAs in Cancer. Cancer Res., 2021, 81(16), 4174-4182.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-4010] [PMID: 34016622]
[29]
Sartorelli, V.; Lauberth, S.M. Enhancer RNAs are an important regulatory layer of the epigenome. Nat. Struct. Mol. Biol., 2020, 27(6), 521-528.
[http://dx.doi.org/10.1038/s41594-020-0446-0] [PMID: 32514177]
[30]
Huang, Z.; Du, G.; Huang, X.; Han, L.; Han, X.; Xu, B.; Zhang, Y.; Yu, M.; Qin, Y.; Xia, Y.; Wang, X.; Lu, C. The enhancer RNA lnc-SLC4A1-1 epigenetically regulates unexplained recurrent pregnancy loss (URPL) by activating CXCL8 and NF-kB pathway. EBioMedicine, 2018, 38, 162-170.
[http://dx.doi.org/10.1016/j.ebiom.2018.11.015] [PMID: 30448228]
[31]
Shen, Y.; Huang, Z.; Yang, R.; Chen, Y.; Wang, Q.; Gao, L. Insights into enhancer RNAs: Biogenesis and emerging role in brain diseases. Neuroscientist, 2023, 29(2), 166-176.
[http://dx.doi.org/10.1177/10738584211046889] [PMID: 34612730]
[32]
Li, W.; Lam, M.T.Y.; Notani, D. Enhancer RNAs. Cell Cycle, 2014, 13(20), 3151-3152.
[http://dx.doi.org/10.4161/15384101.2014.962860] [PMID: 25485487]
[33]
Han, Z.; Li, W. Enhancer RNA: What we know and what we can achieve. Cell Prolif., 2022, 55(4), e13202.
[http://dx.doi.org/10.1111/cpr.13202] [PMID: 35170113]
[34]
Kaikkonen, M.U.; Spann, N.J.; Heinz, S.; Romanoski, C.E.; Allison, K.A.; Stender, J.D.; Chun, H.B.; Tough, D.F.; Prinjha, R.K.; Benner, C.; Glass, C.K. Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol. Cell, 2013, 51(3), 310-325.
[http://dx.doi.org/10.1016/j.molcel.2013.07.010] [PMID: 23932714]
[35]
Andersson, R.; Gebhard, C.; Miguel-Escalada, I.; Hoof, I.; Bornholdt, J.; Boyd, M.; Chen, Y.; Zhao, X.; Schmidl, C.; Suzuki, T.; Ntini, E.; Arner, E.; Valen, E.; Li, K.; Schwarzfischer, L.; Glatz, D.; Raithel, J.; Lilje, B.; Rapin, N.; Bagger, F.O.; Jørgensen, M.; Andersen, P.R.; Bertin, N.; Rackham, O.; Burroughs, A.M.; Baillie, J.K.; Ishizu, Y.; Shimizu, Y.; Furuhata, E.; Maeda, S.; Negishi, Y.; Mungall, C.J.; Meehan, T.F.; Lassmann, T.; Itoh, M.; Kawaji, H.; Kondo, N.; Kawai, J.; Lennartsson, A.; Daub, C.O.; Heutink, P.; Hume, D.A.; Jensen, T.H.; Suzuki, H.; Hayashizaki, Y.; Müller, F.; Forrest, A.R.R.; Carninci, P.; Rehli, M.; Sandelin, A. An atlas of active enhancers across human cell types and tissues. Nature, 2014, 507(7493), 455-461.
[http://dx.doi.org/10.1038/nature12787] [PMID: 24670763]
[36]
Bose, D.A.; Donahue, G.; Reinberg, D.; Shiekhattar, R.; Bonasio, R.; Berger, S.L. RNA binding to CBP stimulates histone acetylation and transcription. Cell, 2017, 168(1-2), 135-149.e22.
[http://dx.doi.org/10.1016/j.cell.2016.12.020] [PMID: 28086087]
[37]
Li, W.; Notani, D.; Ma, Q.; Tanasa, B.; Nunez, E.; Chen, A.Y.; Merkurjev, D.; Zhang, J.; Ohgi, K.; Song, X.; Oh, S.; Kim, H.S.; Glass, C.K.; Rosenfeld, M.G. Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation. Nature, 2013, 498(7455), 516-520.
[http://dx.doi.org/10.1038/nature12210] [PMID: 23728302]
[38]
Bose, D.A.; Berger, S.L. eRNA binding produces tailored CBP activity profiles to regulate gene expression. RNA Biol., 2017, 14(12), 1655-1659.
[http://dx.doi.org/10.1080/15476286.2017.1353862] [PMID: 28891741]
[39]
Jiao, W.; Chen, Y.; Song, H.; Li, D.; Mei, H.; Yang, F.; Fang, E.; Wang, X.; Huang, K.; Zheng, L.; Tong, Q. HPSE enhancer RNA promotes cancer progression through driving chromatin looping and regulating hnRNPU/p300/EGR1/HPSE axis. Oncogene, 2018, 37(20), 2728-2745.
[http://dx.doi.org/10.1038/s41388-018-0128-0] [PMID: 29511351]
[40]
Zhu, M.; Zhang, J.; Li, G.; Liu, Z. ELOVL2-AS1 inhibits migration of triple negative breast cancer. PeerJ, 2022, 10, e13264.
[http://dx.doi.org/10.7717/peerj.13264] [PMID: 35441059]
[41]
He, H.; Li, W.; Wu, D.; Nagy, R.; Liyanarachchi, S.; Akagi, K.; Jendrzejewski, J.; Jiao, H.; Hoag, K.; Wen, B.; Srinivas, M.; Waidyaratne, G.; Wang, R.; Wojcicka, A.; Lattimer, I.R.; Stachlewska, E.; Czetwertynska, M.; Dlugosinska, J.; Gierlikowski, W.; Ploski, R.; Krawczyk, M.; Jazdzewski, K.; Kere, J.; Symer, D.E.; Jin, V.; Wang, Q.; de la Chapelle, A. Ultra-rare mutation in long-range enhancer predisposes to thyroid carcinoma with high penetrance. PLoS One, 2013, 8(5), e61920.
[http://dx.doi.org/10.1371/journal.pone.0061920] [PMID: 23690926]
[42]
Zhou, Y.; Zhou, B.; Pache, L.; Chang, M.; Khodabakhshi, A.H.; Tanaseichuk, O.; Benner, C.; Chanda, S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun., 2019, 10(1), 1523.
[http://dx.doi.org/10.1038/s41467-019-09234-6] [PMID: 30944313]
[43]
Thomas-Chollier, M.; Hufton, A.; Heinig, M.; O’Keeffe, S.; Masri, N.E.; Roider, H.G.; Manke, T.; Vingron, M. Transcription factor binding predictions using TRAP for the analysis of ChIP-seq data and regulatory SNPs. Nat. Protoc., 2011, 6(12), 1860-1869.
[http://dx.doi.org/10.1038/nprot.2011.409] [PMID: 22051799]
[44]
Pavlidis, E.; Sapalidis, K.; Chatzinikolaou, F.; Kesisoglou, I. Medullary thyroid cancer: molecular factors, management and treatment. Rom. J. Morphol. Embryol., 2021, 61(3), 681-686.
[http://dx.doi.org/10.47162/RJME.61.3.06] [PMID: 33817709]
[45]
Arnold, P.R.; Wells, A.D.; Li, X.C. Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate. Front. Cell Dev. Biol., 2020, 7, 377.
[http://dx.doi.org/10.3389/fcell.2019.00377] [PMID: 31993419]
[46]
Wang, Y.; Zhang, C.; Wang, Y.; Liu, X.; Zhang, Z. Enhancer RNA (eRNA) in human diseases. Int. J. Mol. Sci., 2022, 23(19), 11582.
[http://dx.doi.org/10.3390/ijms231911582] [PMID: 36232885]
[47]
Ahmed, I.; Yang, S.H.; Ogden, S.; Zhang, W.; Li, Y.; Sharrocks, A.D. eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways. eLife, 2023, 12, e80840.
[http://dx.doi.org/10.7554/eLife.80840] [PMID: 36803948]
[48]
Riethoven, J.J.M. Regulatory regions in DNA: promoters, enhancers, silencers, and insulators. Methods Mol. Biol., 2010, 674, 33-42.
[http://dx.doi.org/10.1007/978-1-60761-854-6_3] [PMID: 20827584]
[49]
Liang, Y.; Zhang, Q.; Xin, T.; Zhang, D.L. A four-enhancer RNA-based prognostic signature for thyroid cancer. Exp. Cell Res., 2022, 412(2), 113023.
[http://dx.doi.org/10.1016/j.yexcr.2022.113023] [PMID: 35033555]
[50]
Wu, P.; Shi, J.; Wang, Z.; Sun, W.; Zhang, H. Evaluate the immune-related eRNA models and signature score to predict the response to immunotherapy in thyroid carcinoma. Cancer Cell Int., 2022, 22(1), 307.
[http://dx.doi.org/10.1186/s12935-022-02722-8] [PMID: 36217201]
[51]
Zhu, Y.; Sun, L.; Chen, Z.; Whitaker, J.W.; Wang, T.; Wang, W. Predicting enhancer transcription and activity from chromatin modifications. Nucleic Acids Res., 2013, 41(22), 10032-10043.
[http://dx.doi.org/10.1093/nar/gkt826] [PMID: 24038352]
[52]
Kang, Y.; Kim, Y.W.; Kang, J.; Kim, A. Histone H3K4me1 and H3K27ac play roles in nucleosome eviction and eRNA transcription, respectively, at enhancers. FASEB J., 2021, 35(8), e21781.
[http://dx.doi.org/10.1096/fj.202100488R] [PMID: 34309923]
[53]
Liang, M.; Jia, J.; Chen, L.; Wei, B.; Guan, Q.; Ding, Z.; Yu, J.; Pang, R.; He, G. LncRNA MCM3AP-AS1 promotes proliferation and invasion through regulating miR-211-5p/SPARC axis in papillary thyroid cancer. Endocrine, 2019, 65(2), 318-326.
[http://dx.doi.org/10.1007/s12020-019-01939-4] [PMID: 31030335]
[54]
Nian, R.; Li, W.; Li, X.; Zhang, J.; Li, W.; Pan, F.; Cheng, J.; Jin, X. LncRNA MCM3AP-AS1 serves as a competing endogenous RNA of miR-218 to upregulate GLUT1 in papillary thyroid carcinoma. Arch. Endocrinol. Metab., 2022, 67(1), 55-63.
[http://dx.doi.org/10.20945/2359-3997000000510] [PMID: 35929906]
[55]
Moloney, J.N.; Cotter, T.G. ROS signalling in the biology of cancer. Semin. Cell Dev. Biol., 2018, 80, 50-64.
[http://dx.doi.org/10.1016/j.semcdb.2017.05.023] [PMID: 28587975]
[56]
Wang, H.H.; Ma, J.N.; Zhan, X.R. Circular RNA circ_0067934 attenuates ferroptosis of thyroid cancer cells by miR-545-3p/SLC7A11 signaling. Front. Endocrinol. (Lausanne), 2021, 12, 670031.
[http://dx.doi.org/10.3389/fendo.2021.670031] [PMID: 34290668]
[57]
Srinivas, U.S.; Tan, B.W.Q.; Vellayappan, B.A.; Jeyasekharan, A.D. ROS and the DNA damage response in cancer. Redox Biol., 2019, 25, 101084.
[http://dx.doi.org/10.1016/j.redox.2018.101084] [PMID: 30612957]
[58]
Cui, Q.; Wang, J.Q.; Assaraf, Y.G.; Ren, L.; Gupta, P.; Wei, L.; Ashby, C.R., Jr; Yang, D.H.; Chen, Z.S. Modulating ROS to overcome multidrug resistance in cancer. Drug Resist. Updat., 2018, 41, 1-25.
[http://dx.doi.org/10.1016/j.drup.2018.11.001] [PMID: 30471641]
[59]
Cheung, E.C.; Vousden, K.H. The role of ROS in tumour development and progression. Nat. Rev. Cancer, 2022, 22(5), 280-297.
[http://dx.doi.org/10.1038/s41568-021-00435-0] [PMID: 35102280]
[60]
Li, L.; Tan, J.; Miao, Y.; Lei, P.; Zhang, Q. ROS and Autophagy: Interactions and Molecular Regulatory Mechanisms. Cell. Mol. Neurobiol., 2015, 35(5), 615-621.
[http://dx.doi.org/10.1007/s10571-015-0166-x] [PMID: 25722131]
[61]
Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A. ROS in cancer therapy: the bright side of the moon. Exp. Mol. Med., 2020, 52(2), 192-203.
[http://dx.doi.org/10.1038/s12276-020-0384-2] [PMID: 32060354]
[62]
Lee, J.H.; Wang, R.; Xiong, F.; Krakowiak, J.; Liao, Z.; Nguyen, P.T.; Moroz-Omori, E.V.; Shao, J.; Zhu, X.; Bolt, M.J.; Wu, H.; Singh, P.K.; Bi, M.; Shi, C.J.; Jamal, N.; Li, G.; Mistry, R.; Jung, S.Y.; Tsai, K.L.; Ferreon, J.C.; Stossi, F.; Caflisch, A.; Liu, Z.; Mancini, M.A.; Li, W. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Mol. Cell, 2021, 81(16), 3368-3385.e9.
[http://dx.doi.org/10.1016/j.molcel.2021.07.024] [PMID: 34375583]
[63]
Tan, H.; Liu, T.; Zhou, T. Exploring the role of eRNA in regulating gene expression. Math. Biosci. Eng., 2021, 19(2), 2095-2119.
[http://dx.doi.org/10.3934/mbe.2022098] [PMID: 35135243]
[64]
Xiang, L.; Zheng, J.; Zhang, M.; Ai, T.; Cai, B. FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2. Stem Cell Res. Ther., 2020, 11(1), 403.
[http://dx.doi.org/10.1186/s13287-020-01928-9] [PMID: 32943107]
[65]
Li, Y.; Zhang, Y.; Yao, Z.; Li, S.; Yin, Z.; Xu, M. Forkhead box Q1: A key player in the pathogenesis of tumors (Review). Int. J. Oncol., 2016, 49(1), 51-58.
[http://dx.doi.org/10.3892/ijo.2016.3517] [PMID: 27176124]
[66]
Bagati, A.; Bianchi-Smiraglia, A.; Moparthy, S.; Kolesnikova, K.; Fink, E.E.; Kolesnikova, M.; Roll, M.V.; Jowdy, P.; Wolff, D.W.; Polechetti, A.; Yun, D.H.; Lipchick, B.C.; Paul, L.M.; Wrazen, B.; Moparthy, K.; Mudambi, S.; Morozevich, G.E.; Georgieva, S.G.; Wang, J.; Shafirstein, G.; Liu, S.; Kandel, E.S.; Berman, A.E.; Box, N.F.; Paragh, G.; Nikiforov, M.A. FOXQ1 controls the induced differentiation of melanocytic cells. Cell Death Differ., 2018, 25(6), 1040-1049.
[http://dx.doi.org/10.1038/s41418-018-0066-y] [PMID: 29463842]
[67]
Zhang, J.; Liu, Y.; Zhang, J.; Cui, X.; Li, G.; Wang, J.; Ren, H.; Zhang, Y. FOXQ1 promotes gastric cancer metastasis through upregulation of Snail. Oncol. Rep., 2016, 35(6), 3607-3613.
[http://dx.doi.org/10.3892/or.2016.4736] [PMID: 27109028]
[68]
Katoh, M.; Katoh, M. Human FOX gene family (Review). Int. J. Oncol., 2004, 25(5), 1495-1500.
[PMID: 15492844]
[69]
Pizzolato, G.; Moparthi, L.; Söderholm, S.; Cantù, C.; Koch, S. The oncogenic transcription factor FOXQ1 is a differential regulator of Wnt target genes. J. Cell Sci., 2022, 135(19), jcs260082.
[http://dx.doi.org/10.1242/jcs.260082] [PMID: 36124643]
[70]
Mitchell, A.V.; Wu, L.; James Block, C.; Zhang, M.; Hackett, J.; Craig, D.B.; Chen, W.; Zhao, Y.; Zhang, B.; Dang, Y.; Zhang, X.; Zhang, S.; Wang, C.; Gibson, H.; Pile, L.A.; Kidder, B.; Matherly, L.; Yang, Z.; Dou, Y.; Wu, G. FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis. Nat. Commun., 2022, 13(1), 6548.
[http://dx.doi.org/10.1038/s41467-022-34239-z] [PMID: 36319643]
[71]
Yang, M.; Liu, Q.; Dai, M.; Peng, R.; Li, X.; Zuo, W.; Gou, J.; Zhou, F.; Yu, S.; Liu, H.; Huang, M. FOXQ1-mediated SIRT1 upregulation enhances stemness and radio-resistance of colorectal cancer cells and restores intestinal microbiota function by promoting β-catenin nuclear translocation. J. Exp. Clin. Cancer Res., 2022, 41(1), 70.
[http://dx.doi.org/10.1186/s13046-021-02239-4] [PMID: 35183223]
[72]
Liu, J.Y.; Wu, X.Y.; Wu, G.N.; Liu, F.K.; Yao, X.Q. FOXQ1 promotes cancer metastasis by PI3K/AKT signaling regulation in colorectal carcinoma. Am. J. Transl. Res., 2017, 9(5), 2207-2218.
[PMID: 28559972]
[73]
Liu, Z.; Qin, Y.; Dong, S.; Chen, X.; Huo, Z.; Zhen, Z. Overexpression of miR-106a enhances oxaliplatin sensitivity of colorectal cancer through regulation of FOXQ1. Oncol. Lett., 2020, 19(1), 663-670.
[PMID: 31897182]
[74]
Pei, Y.; Wang, P.; Liu, H.; He, F.; Ming, L. FOXQ1 promotes esophageal cancer proliferation and metastasis by negatively modulating CDH1. Biomed. Pharmacother., 2015, 74, 89-94.
[http://dx.doi.org/10.1016/j.biopha.2015.07.010] [PMID: 26349968]
[75]
Li, L.; Xu, B.; Zhang, H.; Wu, J.; Song, Q.; Yu, J. Potentiality of forkhead box Q1 as a biomarker for monitoring tumor features and predicting prognosis in non-small cell lung cancer. J. Clin. Lab. Anal., 2020, 34(1), e23031.
[http://dx.doi.org/10.1002/jcla.23031] [PMID: 31713908]
[76]
Li, P.; Pan, X.; Zheng, Z.; Sun, Y.; Han, Y.; Dong, J.; Lu, M. Downregulation of miR-519d-3p is associated with poor outcomes and facilitates tumor progression in papillary thyroid cancer by regulating FOXQ1. Horm. Metab. Res., 2021, 53(9), 625-632.
[http://dx.doi.org/10.1055/a-1560-2827] [PMID: 34496413]
[77]
Li, Y.; Wang, H.Q.; Wang, A.C.; Li, Y.X.; Ding, S.S.; An, X.J.; Shi, H.Y. Overexpression of forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma. Clin. Endocrinol. (Oxf.), 2019, 90(2), 334-342.
[http://dx.doi.org/10.1111/cen.13896] [PMID: 30378716]