Serous BMP8A has Clinical Significance in the Ultrasonic Diagnosis of Thyroid Cancer and Promotes Thyroid Cancer Cell Progression

Author(s): Kun Liu, Min Gao, Dongdong Qin, Hongjun Wang, Qixiu Lu*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
(Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders)

Volume 20 , Issue 4 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Objective: This study aims to discover a potential cytokine biomarker for early diagnosis of thyroid cancer.

Methods: We employed data mining of The Cancer Genome Atlas (TCGA) and experimentally elucidated its mechanistic contributions. The differential expression genes (DEGs) between thyroid cancer and health population were analyzed with TCGA online bioinformatic tools. The relative expression of Bone Morphogenetic Protein 8A (BMP8A) was determined by real-time PCR in ultrasonic diagnosed thyroid cancer both in vivo and in vitro. The serous BMP8A content was quantified with an ELISA kit. Protein levels of BMP8A, OCLN, ZEB1, EZH2 and β-Actin were analyzed by Western blot. Cell viability was measured by the MTT assay, and anchorage-independent growth was measured by the soft agar colony formation assay. Cell migrative and invasive capacities were interrogated with transwell chamber assays.

Results: We identified aberrantly high expression of BMP8A in thyroid cancer, which was associated with unfavorable prognosis and tumor progression. The serous BMP8A was also significantly up-regulated in thyroid cancer patients. Ectopic over-expression of BMP8A remarkably stimulated cell viability and anchorage-independent growth. Meanwhile, the migrative and invasive capacities were greatly increased in response to BMP8A over-expression. Mechanistically, we characterized the positive correlation between BMP8A and TCF7L1, and forced expression of TCF7L1 induced BMP8A expression in TPC-1 cells.

Conclusion: In summary, we have identified a novel biomarker for early diagnosis in addition to Ultrasound for thyroid cancer, which is subjected to TCF7L1 regulation.

Keywords: Thyroid cancer, BMP8A, diagnosis, biomarker, TCF7L1, ultrasound.

[1]
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]
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[3]
Myung, S.K.; Lee, C.W.; Lee, J.; Kim, J.; Kim, H.S. Risk factors for thyroid cancer: A hospital-based case-control study in korean adults. Cancer Res. Treat., 2017, 49(1), 70-78.
[http://dx.doi.org/10.4143/crt.2015.310] [PMID: 27338034]
[4]
Nikiforov, Y.E. Role of molecular markers in thyroid nodule management: Then and now. Endocr. Pract., 2017, 23(8), 979-988.
[http://dx.doi.org/10.4158/EP171805.RA] [PMID: 28534687]
[5]
Zarkesh, M.; Zadeh-Vakili, A.; Azizi, F.; Foroughi, F.; Akhavan, M.M.; Hedayati, M. Altered epigenetic mechanisms in thyroid cancer subtypes. Mol. Diagn. Ther., 2018, 22(1), 41-56.
[http://dx.doi.org/10.1007/s40291-017-0303-y] [PMID: 28986854]
[6]
Cho, Y.J.; Kim, D.Y.; Park, E.C.; Han, K.T. Thyroid fine-needle aspiration biopsy positively correlates with increased diagnosis of thyroid cancer in South Korean patients. BMC Cancer, 2017, 17(1), 114.
[http://dx.doi.org/10.1186/s12885-017-3104-0] [PMID: 28173779]
[7]
Haugen, B.R. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: What is new and what has changed? Cancer, 2017, 123(3), 372-381.
[http://dx.doi.org/10.1002/cncr.30360] [PMID: 27741354]
[8]
Siravegna, G.; Marsoni, S.; Siena, S.; Bardelli, A. Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol., 2017, 14(9), 531-548.
[http://dx.doi.org/10.1038/nrclinonc.2017.14] [PMID: 28252003]
[9]
Paricharttanakul, N.M.; Saharat, K.; Chokchaichamnankit, D.; Punyarit, P.; Srisomsap, C.; Svasti, J. Unveiling a novel biomarker panel for diagnosis and classification of well-differentiated thyroid carcinomas. Oncol. Rep., 2016, 35(4), 2286-2296.
[http://dx.doi.org/10.3892/or.2016.4567] [PMID: 26782318]
[10]
Zane, M.; Agostini, M.; Enzo, M.V.; Casal Ide, E.; Del Bianco, P.; Torresan, F.; Merante Boschin, I.; Pennelli, G.; Saccani, A.; Rubello, D.; Nitti, D.; Pelizzo, M.R. Circulating cell-free DNA, SLC5A8 and SLC26A4 hypermethylation, BRAF(V600E): A non-invasive tool panel for early detection of thyroid cancer. Biomed. Pharmacother., 2013, 67(8), 723-730.
[http://dx.doi.org/10.1016/j.biopha.2013.06.007] [PMID: 23931930]
[11]
Machens, A.; Lorenz, K.; Dralle, H. Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J. Clin. Endocrinol. Metab., 2014, 99(8), 2986-2994.
[http://dx.doi.org/10.1210/jc.2014-1278] [PMID: 24840813]
[12]
Lee, J.C.; Zhao, J.T.; Gundara, J.; Serpell, J.; Bach, L.A.; Sidhu, S. Papillary thyroid cancer-derived exosomes contain miRNA-146b and miRNA-222. J. Surg. Res., 2015, 196(1), 39-48.
[http://dx.doi.org/10.1016/j.jss.2015.02.027] [PMID: 25819770]
[13]
Zhang, Z.Z.; Chen, Q.; Kong, C.Y.; Li, Z.M.; Wang, L.S. Circulating thyroid stimulating hormone receptor messenger RNA and differentiated thyroid cancer: A diagnostic meta-analysis. Oncotarget, 2017, 8(4), 6623-6629.
[http://dx.doi.org/10.18632/oncotarget.14251] [PMID: 28036261]
[14]
Geraldo, M.V.; Kimura, E.T. Integrated analysis of thyroid cancer public datasets reveals role of post-transcriptional regulation on tumor progression by targeting of immune system mediators. PLoS One, 2015, 10(11) e0141726
[http://dx.doi.org/10.1371/journal.pone.0141726] [PMID: 26536459]
[15]
Wu, F.J.; Lin, T.Y.; Sung, L.Y.; Chang, W.F.; Wu, P.C.; Luo, C.W. BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia. Sci. Signal., 2017, 10(477) eaal1910
[http://dx.doi.org/10.1126/scisignal.aal1910] [PMID: 28465413]
[16]
Singh, V.; Singh, L.C.; Vasudevan, M.; Chattopadhyay, I.; Borthakar, B.B.; Rai, A.K.; Phukan, R.K.; Sharma, J.; Mahanta, J.; Kataki, A.C.; Kapur, S.; Saxena, S. Esophageal cancer epigenomics and integrome analysis of genome-wide methylation and expression in high risk northeast Indian population. OMICS, 2015, 19(11), 688-699.
[http://dx.doi.org/10.1089/omi.2015.0121] [PMID: 26496483]
[17]
Mahoney, S.E.; Yao, Z.; Keyes, C.C.; Tapscott, S.J.; Diede, S.J. Genome-wide DNA methylation studies suggest distinct DNA methylation patterns in pediatric embryonal and alveolar rhabdomyosarcomas. Epigenetics, 2012, 7(4), 400-408.
[http://dx.doi.org/10.4161/epi.19463] [PMID: 22419069]
[18]
Zekri, A.R.; Hafez, M.M.; Bahnassy, A.A.; Hassan, Z.K.; Mansour, T.; Kamal, M.M.; Khaled, H.M. Genetic profile of Egyptian hepatocellular-carcinoma associated with hepatitis C virus Genotype 4 by 15 K cDNA microarray: preliminary study. BMC Res. Notes, 2008, 1, 106.
[http://dx.doi.org/10.1186/1756-0500-1-106] [PMID: 18959789]
[19]
Cevallos, R.R.; Rodríguez-Martínez, G.; Gazarian, K. Wnt/β-Catenin/TCF pathway is a phase-dependent promoter of colony formation and mesendodermal differentiation during human somatic cell reprogramming. Stem Cells, 2018, 36(5), 683-695.
[http://dx.doi.org/10.1002/stem.2788] [PMID: 29359466]
[20]
Murphy, M.; Chatterjee, S.S.; Jain, S.; Katari, M.; DasGupta, R. TCF7L1 Modulates Colorectal Cancer Growth by Inhibiting Expression of the Tumor-Suppressor Gene EPHB3. Sci. Rep., 2016, 6, 28299.
[http://dx.doi.org/10.1038/srep28299] [PMID: 27333864]
[21]
Shah, M.; Rennoll, S.A.; Raup-Konsavage, W.M.; Yochum, G.S. A dynamic exchange of TCF3 and TCF4 transcription factors controls MYC expression in colorectal cancer cells. Cell Cycle, 2015, 14(3), 323-332.
[http://dx.doi.org/10.4161/15384101.2014.980643] [PMID: 25659031]
[22]
Chiaro, C.; Lazarova, D.L.; Bordonaro, M. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells. Biochem. Biophys. Res. Commun., 2012, 428(1), 121-126.
[http://dx.doi.org/10.1016/j.bbrc.2012.10.018] [PMID: 23063976]
[23]
Balaz, P.; Plaschke, J.; Krüger, S.; Görgens, H.; Schackert, H.K. TCF-3, 4 protein expression correlates with beta-catenin expression in MSS and MSI-H colorectal cancer from HNPCC patients but not in sporadic colorectal cancers. Int. J. Colorectal Dis., 2010, 25(8), 931-939.
[http://dx.doi.org/10.1007/s00384-010-0959-9] [PMID: 20532534]
[24]
Slyper, M.; Shahar, A.; Bar-Ziv, A.; Granit, R.Z.; Hamburger, T.; Maly, B.; Peretz, T.; Ben-Porath, I. Control of breast cancer growth and initiation by the stem cell-associated transcription factor TCF3. Cancer Res., 2012, 72(21), 5613-5624.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0119] [PMID: 23090119]
[25]
Ku, A.T.; Shaver, T.M.; Rao, A.S.; Howard, J.M.; Rodriguez, C.N.; Miao, Q.; Garcia, G.; Le, D.; Yang, D.; Borowiak, M.; Cohen, D.N.; Chitsazzadeh, V.; Diwan, A.H.; Tsai, K.Y.; Nguyen, H. TCF7L1 promotes skin tumorigenesis independently of β-catenin through induction of LCN2. eLife, 2017, 6e, 23242.
[http://dx.doi.org/10.7554/eLife.23242] [PMID: 28467300]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 4
Year: 2020
Page: [591 - 598]
Pages: 8
DOI: 10.2174/1871530319666191018170022
Price: $65

Article Metrics

PDF: 18
HTML: 2
EPUB: 1
PRC: 1