Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

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

Research Article

LINC00891 Promotes Tumorigenesis and Metastasis of Thyroid Cancer by Regulating SMAD2/3 via EZH2

Author(s): Yuhao Si, Jialiang Wen, Chunlei Hu, Hao Chen, Lizhi Lin, Yiying Xu, Disuo Ren, Xinyu Meng, Yinghao Wang, Erjie Xia, Adheesh Bhandari* and Ouchen Wang*

Volume 31, Issue 24, 2024

Published on: 04 April, 2024

Page: [3818 - 3833] Pages: 16

DOI: 10.2174/0929867330666230522115945

Price: $65

conference banner
Abstract

Background: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays.

Methods: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression was correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion and prompt apoptosis and G1 arrest of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting.

Results: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown.

Conclusion: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

[1]
Trigo, J.M.; Capdevila, J.; Grande, E.; Grau, J.; Lianes, P. Thyroid cancer: SEOM clinical guidelines. Clin. Transl. Oncol., 2014, 16(12), 1035-1042.
[http://dx.doi.org/10.1007/s12094-014-1224-4] [PMID: 25245079]
[2]
Li, M.; Maso, L.D.; Vaccarella, S. Global trends in thyroid cancer incidence and the impact of overdiagnosis. Lancet Diabetes Endocrinol., 2020, 8(6), 468-470.
[http://dx.doi.org/10.1016/S2213-8587(20)30115-7] [PMID: 32445733]
[3]
Miranda-Filho, A.; Lortet-Tieulent, J.; Bray, F.; Cao, B.; Franceschi, S.; Vaccarella, S.; Dal Maso, L. Thyroid cancer incidence trends by histology in 25 countries: A population-based study. Lancet Diabetes Endocrinol., 2021, 9(4), 225-234.
[http://dx.doi.org/10.1016/S2213-8587(21)00027-9] [PMID: 33662333]
[4]
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]
[5]
Zhang, S.; Sun, K.; Zheng, R.; Zeng, H.; Wang, S.; Chen, R.; Wei, W.; He, J. Cancer incidence and mortality in China, 2015. J. Natl. Cancer Inst., 2021, 1(1), 2-11.
[http://dx.doi.org/10.1016/j.jncc.2020.12.001]
[6]
Mirian, C.; Grønhøj, C.; Jensen, D.H.; Jakobsen, K.K.; Karnov, K.; Jensen, J.S.; Hahn, C.H.; Klitmøller, T.A.; Bentzen, J.; von Buchwald, C. Trends in thyroid cancer: Retrospective analysis of incidence and survival in Denmark 1980–2014. Cancer Epidemiol., 2018, 55, 81-87.
[http://dx.doi.org/10.1016/j.canep.2018.05.009] [PMID: 29852396]
[7]
Shaha, A. Treatment of thyroid cancer based on risk groups. J. Surg. Oncol., 2006, 94(8), 683-691.
[http://dx.doi.org/10.1002/jso.20697] [PMID: 17131422]
[8]
Sampson, E.; Brierley, J.D.; Le, L.W.; Rotstein, L.; Tsang, R.W. Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis. Cancer, 2007, 110(7), 1451-1456.
[http://dx.doi.org/10.1002/cncr.22956] [PMID: 17705176]
[9]
Marchese, F.P.; Raimondi, I.; Huarte, M. The multidimensional mechanisms of long noncoding RNA function. Genome Biol., 2017, 18(1), 206.
[http://dx.doi.org/10.1186/s13059-017-1348-2] [PMID: 29084573]
[10]
Kang, W.; Wang, Q.; Dai, Y.; Wang, H.; Wang, M.; Wang, J.; Zhang, D.; Sun, P.; Qi, T.; Jin, X.; Cui, Z. Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis. Cell Death Dis., 2020, 11(12), 1038.
[http://dx.doi.org/10.1038/s41419-020-03240-z] [PMID: 33288752]
[11]
Chang, K.C.; Diermeier, S.D.; Yu, A.T.; Brine, L.D.; Russo, S.; Bhatia, S.; Alsudani, H.; Kostroff, K.; Bhuiya, T.; Brogi, E.; Pappin, D.J.; Bennett, C.F.; Rigo, F.; Spector, D.L. MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression. Nat. Commun., 2020, 11(1), 6438.
[http://dx.doi.org/10.1038/s41467-020-20207-y] [PMID: 33353933]
[12]
Cai, H.; Yu, Y.; Ni, X.; Li, C.; Hu, Y.; Wang, J.; Chen, F.; Xi, S.; Chen, Z. LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis. Cell Death Dis., 2020, 11(12), 1032.
[http://dx.doi.org/10.1038/s41419-020-03247-6] [PMID: 33268783]
[13]
Guo, K.; Qian, K.; Shi, Y.; Sun, T.; Wang, Z. LncRNA-MIAT promotes thyroid cancer progression and function as ceRNA to target EZH2 by sponging miR-150-5p. Cell Death Dis., 2021, 12(12), 1097.
[http://dx.doi.org/10.1038/s41419-021-04386-0] [PMID: 34811354]
[14]
Ye, M.; Dong, S.; Hou, H.; Zhang, T.; Shen, M. Oncogenic role of long noncoding RNAMALAT1 in thyroid cancer progression through regulation of the miR-204/IGF2BP2/m6A-MYC signaling. Mol. Ther. Nucleic Acids, 2021, 23, 1-12.
[http://dx.doi.org/10.1016/j.omtn.2020.09.023] [PMID: 33312756]
[15]
Chen, B.J.; Byrne, F.L.; Takenaka, K.; Modesitt, S.C.; Olzomer, E.M.; Mills, J.D.; Farrell, R.; Hoehn, K.L.; Janitz, M. Transcriptome landscape of long intergenic non-coding RNAs in endometrial cancer. Gynecol. Oncol., 2017, 147(3), 654-662.
[http://dx.doi.org/10.1016/j.ygyno.2017.10.006] [PMID: 29050779]
[16]
Ma, X.; Li, Y.; Song, Y.; Xu, G. Long noncoding RNA CCDC26 promotes thyroid cancer malignant progression via miR-422a/EZH2/Sirt6 Axis. OncoTargets Ther., 2021, 14, 3083-3094.
[http://dx.doi.org/10.2147/OTT.S282011] [PMID: 34007185]
[17]
Wang, L.J.; Sun, G.Z.; Chen, Y.F. LncRNA MSTO2P promotes proliferation and autophagy of lung cancer cells by up-regulating EZH2 expression. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(8), 3375-3382.
[http://dx.doi.org/10.26355/eurrev_201904_17701] [PMID: 31081092]
[18]
Xu, M.; Chen, X.; Lin, K.; Zeng, K.; Liu, X.; Xu, X.; Pan, B.; Xu, T.; Sun, L.; He, B.; Pan, Y.; Sun, H.; Wang, S. lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer. J. Hematol. Oncol., 2019, 12(1), 3.
[http://dx.doi.org/10.1186/s13045-018-0690-5] [PMID: 30626446]
[19]
Wu, Y.; Hu, L.; Liang, Y.; Li, J.; Wang, K.; Chen, X.; Meng, H.; Guan, X.; Yang, K.; Bai, Y. Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2. Mol. Cancer, 2017, 16(1), 150.
[http://dx.doi.org/10.1186/s12943-017-0715-7] [PMID: 28854977]
[20]
Barros-Filho, M.C.; de Mello, J.B.H.; Marchi, F.A.; Pinto, C.A.L.; da Silva, I.C.; Damasceno, P.K.F.; Soares, M.B.P.; Kowalski, L.P.; Rogatto, S.R. GADD45B transcript is a prognostic marker in papillary thyroid carcinoma patients treated with total thyroidectomy and radioiodine therapy. Front. Endocrinol., 2020, 11, 269.
[http://dx.doi.org/10.3389/fendo.2020.00269] [PMID: 32425887]
[21]
Barros-Filho, M.C.; Marchi, F.A.; Pinto, C.A.; Rogatto, S.R.; Kowalski, L.P. High diagnostic accuracy based on CLDN10, HMGA2, and LAMB3 transcripts in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab., 2015, 100(6), E890-E899.
[http://dx.doi.org/10.1210/jc.2014-4053] [PMID: 25867809]
[22]
Jiang, H.; Wong, W.H. SeqMap: Mapping massive amount of oligonucleotides to the genome. Bioinformatics, 2008, 24(20), 2395-2396.
[http://dx.doi.org/10.1093/bioinformatics/btn429] [PMID: 18697769]
[23]
Troyanskaya, O.; Cantor, M.; Sherlock, G.; Brown, P.; Hastie, T.; Tibshirani, R.; Botstein, D.; Altman, R.B. Missing value estimation methods for DNA microarrays. Bioinformatics, 2001, 17(6), 520-525.
[http://dx.doi.org/10.1093/bioinformatics/17.6.520] [PMID: 11395428]
[24]
Subramanian, A.; Tamayo, P.; Mootha, V.K.; Mukherjee, S.; Ebert, B.L.; Gillette, M.A.; Paulovich, A.; Pomeroy, S.L.; Golub, T.R.; Lander, E.S.; Mesirov, J.P. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA, 2005, 102(43), 15545-15550.
[http://dx.doi.org/10.1073/pnas.0506580102] [PMID: 16199517]
[25]
Tang, Z.; Li, C.; Kang, B.; Gao, G.; Li, C.; Zhang, Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res., 2017, 45(W1), W98-W102.
[http://dx.doi.org/10.1093/nar/gkx247] [PMID: 28407145]
[26]
Wu, N.; Jiang, M.; Liu, H.; Chu, Y.; Wang, D.; Cao, J.; Wang, Z.; Xie, X.; Han, Y.; Xu, B. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-β/SMAD2/3 signaling pathway. Cell Death Differ., 2021, 28(1), 219-232.
[http://dx.doi.org/10.1038/s41418-020-0596-y] [PMID: 32737443]
[27]
Li, H.; Zhang, Z.; Chen, L.; Sun, X.; Zhao, Y.; Guo, Q.; Zhu, S.; Li, P.; Min, L.; Zhang, S. Cytoplasmic Asporin promotes cell migration by regulating TGF-β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer. Cell Death Dis., 2019, 10(2), 109.
[http://dx.doi.org/10.1038/s41419-019-1376-9] [PMID: 30728352]
[28]
Zhang, B.; Ye, H.; Ren, X.; Zheng, S.; Zhou, Q.; Chen, C.; Lin, Q.; Li, G.; Wei, L.; Fu, Z.; Zhang, Y.; Hu, C.; Li, Z.; Chen, R. Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. Cancer Lett., 2019, 459, 204-215.
[http://dx.doi.org/10.1016/j.canlet.2019.06.005] [PMID: 31199988]
[29]
Zhong, F.J.; Sun, B.; Cao, M.M.; Xu, C.; Li, Y.M.; Yang, L.Y. STMN2 mediates nuclear translocation of Smad2/3 and enhances TGFβ signaling by destabilizing microtubules to promote epithelial-mesenchymal transition in hepatocellular carcinoma. Cancer Lett., 2021, 506, 128-141.
[http://dx.doi.org/10.1016/j.canlet.2021.03.001] [PMID: 33705863]
[30]
Duan, R.; Du, W.; Guo, W. EZH2: A novel target for cancer treatment. J. Hematol. Oncol., 2020, 13(1), 104.
[http://dx.doi.org/10.1186/s13045-020-00937-8] [PMID: 32723346]
[31]
Zhang, Y.; Song, D.; Peng, Z.; Wang, R.; Li, K.; Ren, H.; Sun, X.; Du, N.; Tang, S.C. LINC00891 regulated by miR-128-3p/GATA2 axis impedes lung cancer cell proliferation, invasion and EMT by inhibiting RhoA pathway. Acta Biochim. Biophys. Sin. (Shanghai), 2022, 54(3), 378-387.
[http://dx.doi.org/10.3724/abbs.2022005] [PMID: 35538035]
[32]
Zhou, B.; Guo, W.; Sun, C.; Zhang, B.; Zheng, F. Linc00462 promotes pancreatic cancer invasiveness through the miR-665/TGFBR1-TGFBR2/SMAD2/3 pathway. Cell Death Dis., 2018, 9(6), 706.
[http://dx.doi.org/10.1038/s41419-018-0724-5] [PMID: 29899418]
[33]
Yang, J.; Antin, P.; Berx, G.; Blanpain, C.; Brabletz, T.; Bronner, M.; Campbell, K.; Cano, A.; Casanova, J.; Christofori, G.; Dedhar, S.; Derynck, R.; Ford, H.L.; Fuxe, J.; García de Herreros, A.; Goodall, G.J.; Hadjantonakis, A.K.; Huang, R.Y.J.; Kalcheim, C.; Kalluri, R.; Kang, Y.; Khew-Goodall, Y.; Levine, H.; Liu, J.; Longmore, G.D.; Mani, S.A.; Massagué, J.; Mayor, R.; McClay, D.; Mostov, K.E.; Newgreen, D.F.; Nieto, M.A.; Puisieux, A.; Runyan, R.; Savagner, P.; Stanger, B.; Stemmler, M.P.; Takahashi, Y.; Takeichi, M.; Theveneau, E.; Thiery, J.P.; Thompson, E.W.; Weinberg, R.A.; Williams, E.D.; Xing, J.; Zhou, B.P.; Sheng, G. Guidelines and definitions for research on epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol., 2020, 21(6), 341-352.
[http://dx.doi.org/10.1038/s41580-020-0237-9] [PMID: 32300252]
[34]
Pastushenko, I.; Blanpain, C. EMT transition states during tumor progression and metastasis. Trends Cell Biol., 2019, 29(3), 212-226.
[http://dx.doi.org/10.1016/j.tcb.2018.12.001] [PMID: 30594349]
[35]
Mittal, V. Epithelial mesenchymal transition in tumor metastasis. Annu. Rev. Pathol., 2018, 13(1), 395-412.
[http://dx.doi.org/10.1146/annurev-pathol-020117-043854] [PMID: 29414248]
[36]
Carneiro, B.A.; El-Deiry, W.S. Targeting apoptosis in cancer therapy. Nat. Rev. Clin. Oncol., 2020, 17(7), 395-417.
[http://dx.doi.org/10.1038/s41571-020-0341-y] [PMID: 32203277]
[37]
Mirzaei, S.; Gholami, M.H.; Hushmandi, K.; Hashemi, F.; Zabolian, A.; Canadas, I.; Zarrabi, A.; Nabavi, N.; Aref, A.R.; Crea, F.; Wang, Y.; Ashrafizadeh, M.; Kumar, A.P. The long and short non-coding RNAs modulating EZH2 signaling in cancer. J. Hematol. Oncol., 2022, 15(1), 18.
[http://dx.doi.org/10.1186/s13045-022-01235-1] [PMID: 35236381]
[38]
Li, Y.; Wan, Q.; Wang, W.; Mai, L.; Sha, L.; Mashrah, M.; Lin, Z.; Pan, C. LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis. Biomed. Pharmacother., 2019, 112, 108719.
[http://dx.doi.org/10.1016/j.biopha.2019.108719] [PMID: 30970517]
[39]
Chen, M.J.; Deng, J.; Chen, C.; Hu, W.; Yuan, Y.C.; Xia, Z.K. LncRNA H19 promotes epithelial mesenchymal transition and metastasis of esophageal cancer via STAT3/EZH2 axis. Int. J. Biochem. Cell Biol., 2019, 113, 27-36.
[http://dx.doi.org/10.1016/j.biocel.2019.05.011] [PMID: 31102664]

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