Research Article| Volume 58, ISSUE 4, P437-442, May 2020

Identification of a potential target for treatment of squamous cell carcinoma of the tongue: follistatin

Published:February 27, 2020DOI:


      Squamous cell carcinoma (SCC) of the tongue is the most common oral cancer and is prone to develop regional lymph nodes and distant metastases. Reliable and stable therapeutic targets can improve the curative effect and reduce toxic side effects caused by traditional treatments such as surgery, radiotherapy, and chemotherapy. We have analysed three sets of series of functional gene expression of SCC of the tongue from gene expression omnibus (GEO) datasets, and 154 common differentially expressed genes (DEG) between SCC of the tongue and the corresponding normal tissues were screened. Further bioinformatics research that was based on the data from the Cancer genome atlas, Gene ontology, and the Kyoto encyclopaedia of genes and genomes indicated that the increased expression of follistatin might be correlated with a poor prognosis in these patients. By assay of colony formation, reverse transcription polymerase chain reaction (RT-PCR), western blotting, immunohistochemical staining, and lentivirus transfection, we confirmed that downregulation of follistatin inhibited the proliferation of SCC cells in the tongue.

      Graphical abstract


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        • Byers R.M.
        • El-Naggar A.K.
        • Lee Y.Y.
        • et al.
        Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?.
        Head Neck. 1998; 20: 138-144
        • Zohdi I.
        • El Sharkawy L.S.
        • El Bestar M.F.
        • et al.
        Selective neck dissection (IIa, III): a rational replacement for extended supraomohyoid neck dissection in patients with N0 supraglottic and glottic squamous cell carcinoma.
        Clin Med Insights Ear Nose Throat. 2015; 8: 1-6
        • Huang S.F.
        • Kang C.J.
        • Lin C.Y.
        • et al.
        Neck treatment of patients with early stage oral tongue cancer: comparison between observation, supraomohyoid dissection, and extended dissection.
        Cancer. 2008; 112: 1066-1075
        • Ferlito A.
        • Mannara G.M.
        • Rinaldo A.
        • et al.
        Is extended selective supraomohyoid neck dissection indicated for treatment of oral cancer with clinically negative neck?.
        Acta Otolaryngol. 2000; 120: 792-795
        • Bello I.O.
        • Soini Y.
        • Salo T.
        Prognostic evaluation of oral tongue cancer: means, markers and perspectives (I).
        Oral Oncol. 2010; 46: 630-635
        • Peggs K.
        • Mackinnon S.
        Imatinib mesylate—the new gold standard for treatment of chronic myeloid leukemia.
        N Engl J Med. 2003; 348: 1048-1050
        • Apperley J.F.
        • Gardembas M.
        • Melo J.V.
        • et al.
        Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.
        N Engl J Med. 2002; 347: 481-487
        • Liu Y.
        • Jiang H.
        • Zhou H.
        • et al.
        Lentivirus-mediated silencing of HOTAIR lncRNA restores gefitinib sensitivity by activating Bax/Caspase-3 and suppressing TGF-alpha/EGFR signaling in lung adenocarcinoma.
        Oncol Lett. 2018; 15: 2829-2838
        • Li Y.Q.
        • Liu Y.S.
        • Ying X.W.
        • et al.
        Lentivirus-mediated disintegrin and metalloproteinase 17 RNA interference reversed the acquired resistance to gefitinib in lung adenocarcinoma cells in vitro.
        Biotechnol Prog. 2018; 34: 196-205
        • Lin K.H.
        • Hong S.T.
        • Wang H.T.
        • et al.
        Enhancing anticancer effect of gefitinib across the blood-brain barrier model using liposomes modified with one alpha-helical cell-penetrating peptide or glutathione and Tween 80.
        Int J Mol Sci. 2016; 17 (pii: E1998)
      1. Gene expression omnibus. Available from IRL: Last accessed 28 January 2020.

        • Enokida T.
        • Fujii S.
        • Takahashi M.
        • et al.
        Gene expression profiling to predict recurrence of advanced squamous cell carcinoma of the tongue: discovery and external validation.
        Oncotarget. 2017; 8: 61786-61799
        • Tuch B.B.
        • Laborde R.R.
        • Xu X.
        • et al.
        Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.
        PLoS One. 2010; 5: e9317
        • Estilo C.L.
        • O-charoenrat P.
        • Talbot S.
        • et al.
        Oral tongue cancer gene expression profiling: identification of novel potential prognosticators by oligonucleotide microarray analysis.
        BMC Cancer. 2009; 9: 11
        • Ye H.
        • Yu T.
        • Temam S.
        • et al.
        Transcriptomic dissection of tongue squamous cell carcinoma.
        BMC Genomics. 2008; 9: 69
      2. Cancer genome atlas. Available from URL: Last accessed 6 February 2020.

      3. Gene ontology. Available from URL: Last accessed 29 January 2020.

      4. Kyoto encyclopedia of genes and genomes. Available from URL: Last accessed 6 February 2020.

        • Sun L.
        • Dong S.
        • Ge Y.
        • et al.
        DiVenn: an interactive and integrated web-based visualization tool for comparing gene lists.
        Front Genet. 2019; 10: 421
        • The Cancer Genome Atlas Network
        Comprehensive genomic characterization of head and neck squamous cell carcinomas.
        Nature. 2015; 517: 576-582
        • Lu Z.
        • He Q.
        • Liang J.
        • et al.
        miR-31-5p is a potential circulating biomarker and therapeutic target for oral cancer.
        Mol Ther Nucleic Acids. 2019; 16: 471-480
        • Livak K.J.
        • Schmittgen T.D.
        Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.
        Methods. 2001; 25: 402-408
        • He Q.
        • Chen Z.
        • Cabay R.J.
        • et al.
        microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection.
        Oral Oncol. 2016; 57: 15-20
        • Jiang L.
        • Dai Y.
        • Liu X.
        • et al.
        Identification and experimental validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2) as a microRNA-138 target in tongue squamous cell carcinoma.
        Hum Genet. 2011; 129: 189-197
        • Pascal T.A.
        • Abrol R.
        • Mittal R.
        • et al.
        Experimental validation of the predicted binding site of Escherichia coli K1 outer membrane protein A to human brain microvascular endothelial cells: identification of critical mutations that prevent E. coli meningitis.
        J Biol Chem. 2010; 285: 37753-37761
        • Rappaport S.
        • Fishilevich S.
        • Nadel R.
        Rational confederation of genes and diseases: NGS interpretation via GeneCards, MalaCards and VarElect.
        Biomed Eng. 2017; 16: 72
        • Fishilevich S.
        • Zimmerman S.
        • Kohn A.
        • et al.
        Genic insights from integrated human proteomics in GeneCards.
        Database (Oxford). 2016; (pii: baw030)
        • McPherson S.J.
        • Mellor S.L.
        • Wang H.
        • et al.
        Expression of activin A and follistatin core proteins by human prostate tumor cell lines.
        Endocrinology. 1999; 140: 5303-5309
        • Sulyok S.
        • Wankell M.
        • Alzheimer C.
        • et al.
        Activin: an important regulator of wound repair, fibrosis, and neuroprotection.
        Mol Cell Endocrinol. 2004; 225: 127-132
        • Hashimoto O.
        • Kawasaki N.
        • Tsuchida K.
        • et al.
        Difference between follistatin isoforms in the inhibition of activin signalling: activin neutralizing activity of follistatin isoforms is dependent on their affinity for activin.
        Cell Signal. 2000; 12: 565-571
        • Lerch T.F.
        • Shimasaki S.
        • Woodruff T.K.
        • et al.
        Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions.
        J Biol Chem. 2007; 282: 15930-15939
        • Saucedo L.J.
        • Edgar B.A.
        Filling out the Hippo pathway.
        Nat Rev Mol Cell Biol. 2007; 8: 613-621