Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO
Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO
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DOI：
10.1007/s00432-021-03568-9
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发表时间：
2021-02
影响因子：
3.6
通讯作者：
T. Sasahira;Miyako Kurihara-Shimomura;Hiroyuki Shimomura;A. Bosserhoff;T. Kirita
中科院分区：
文献类型：
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作者：
T. Sasahira;Miyako Kurihara-Shimomura;Hiroyuki Shimomura;A. Bosserhoff;T. Kirita
目的运输和高尔基组织蛋白1(Tango)促进口腔鳞状细胞癌(OSCC)的血管生成和淋巴管生成。为了阐明其潜在的机制，本研究旨在鉴定和鉴定参与口腔鳞状细胞癌的探戈基因下游元件。结果口腔鳞癌组织中粘蛋白20(MUC20)和富含小脯氨酸蛋白1B(SPRR1B)的表达分别下调或上调。MUC20通过改变基质金属蛋白酶-2和E-钙粘蛋白的表达及c-met的磷酸化，增加口腔鳞癌细胞的生长和侵袭力。MUC20通过激活血管内皮生长因子A和C诱导血管生成和淋巴管生成。在高分化口腔鳞癌中，SPRR1B高表达(P= 0.0091)，与角化标志物相关，并通过诱导丝裂原活化蛋白激酶p38磷酸化促进增殖。MUC20的表达与临床分期(P= 0.0024)、淋巴结转移(P= 0.0036)、血管和淋巴管数目(P<； 0.0001)显著相关。结论位于探戈下游的MUC20和SPRR1B基因可作为口腔鳞癌的分子标记，其预后明显低于不表达MUC20的患者(P<； 0.0001)。
PurposeTransport and Golgi organization protein 1 (TANGO) promotes angiogenesis and lymphangiogenesis in oral squamous cell carcinoma (OSCC). To elucidate the underlying mechanisms, this study aims to identify and characterize elements downstream of TANGO that mediate its involvement in OSCC.MethodsIn this study, microarray analysis compared gene expression between control andTANGO-repressed HSC3 cells. Protein expression in 213 OSCC tissue samples was analyzed immunohistochemically.ResultsTANGOrepression decreased or increased expression of Mucin 20 (MUC20) and small proline-rich protein 1B (SPRR1B), respectively. MUC20 increased the growth and invasiveness of OSCC cells via altered matrix metalloproteinase (MMP)-2 and E-cadherin expression and c-met phosphorylation. MUC20 induced angiogenesis and lymphangiogenesis by activating vascular endothelial growth factors A and C. In well-differentiated OSCC, SPRR1B expression was high (P= 0.0091) and correlated with keratinization markers and promoted proliferation by inducing mitogen-activated protein kinase p38 phosphorylation. MUC20 expression correlated significantly with clinical stage (P= 0.0024), lymph node metastasis (P= 0.0036), and number of blood and lymph vessels (P< 0.0001). MUC20-expressing cases had a significantly worse prognosis than non-expressing cases (P< 0.0001).ConclusionMUC20 and SPRR1B located downstream of TANGO may be useful molecular markers for OSCC.