The leucine zipper downregulated in cancer 1 (LDOC1) has been proposed as a regulator of transcription and cell signaling. We have previously demonstrated that LDOC1 is differentially expressed in papillary thyroid carcinoma (PTC), this study was designed to characterize LDOC1 expression in thyroid follicle originated cancer tissues and to specifically evaluate its function in thyroid carcinogenesis. LDOC1 expression was performed in human normal thyroid and thyroid cancer. LDOC1 function was characterized, in two PTC cell lines (TPC1 and BCPAP), through the analysis of in vitro cell proliferation, apoptosis, migration, and invasion along with in vivo tumor xenograft growth. Transduced BCPAP cells were stimulated with tumor necrosis factor α, and the levels of nuclear P65, Bax, Bcl‐2, c‐Myc, and XIAP were assessed. A luciferase reporter assay was used to measure nuclear factor‐κB (NF‐κB) activity, and the functional connection between LDOC1 effect and NF‐κB activity was determined using a specific NF‐κB inhibitor. Our results revealed that LDOC1 was translocated from the nucleus to the cytoplasm in human thyroid cancer, and was significantly downregulated in PTC compared with normal thyroid. LDOC1 overexpression in TPC1 resulted in a significant suppression of the malignant phenotype, whereas LDOC1 ablation in BCPAP promoted this phenotype. Additional studies demonstrated that LDOC1 ablation facilitated nuclear P65 expression and NF‐κB activity. NF‐κB inhibition reversed the effects of LDOC1 ablation on proliferation, apoptosis, migration, and invasion. Our findings confirmed that LDOC1 is a novel therapeutic target in PTC and provides new insight into the role of LDOC1 in PTC progression, through NF‐κΒ signaling suppression.

中文翻译：

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LDOC1在甲状腺癌中差异表达，并在甲状腺乳头状癌中显示肿瘤抑制功能

已提出在癌症1（LDOC1）中下调的亮氨酸拉链作为转录和细胞信号转导的调节剂。我们先前已经证明LDOC1在甲状腺乳头状癌（PTC）中差异表达，该研究旨在表征LDOC1在甲状腺滤泡来源的癌组织中的表达，并专门评估其在甲状腺癌变过程中的功能。LDOC1表达在人类正常甲状腺和甲状腺癌中进行。通过分析体外细胞增殖，凋亡，迁移和侵袭以及体内肿瘤异种移植物生长，在两种PTC细胞系（TPC1和BCPAP）中表征了LDOC1的功能。用肿瘤坏死因子α刺激转导的BCPAP细胞，并评估核P65，Bax，Bcl-2，c-Myc和XIAP的水平。使用萤光素酶报告基因测定法测量核因子κB（NF-κB）活性，并使用特定的NF-κB抑制剂确定LDOC1效应与NF-κB活性之间的功能联系。我们的结果表明，LDOC1在人甲状腺癌中从细胞核转移到细胞质，与正常甲状腺相比，PTC中的LDOC1明显下调。LPC1在TPC1中的过表达导致对恶性表型的显着抑制，而BCPAP中的LDOC1消融促进了这种表型。其他研究表明，LDOC1消融促进了核P65表达和NF-κB活性。NF-κB抑制作用逆转了LDOC1消融对增殖，凋亡，迁移和侵袭的影响。