UHRF1 suppression promotes cell differentiation and reduces inflammatory reaction in anaplastic thyroid cancer.
UHRF1 suppression promotes cell differentiation and reduces inflammatory reaction in anaplastic thyroid cancer.
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UHRF1 抑制可促进细胞分化并减少未分化甲状腺癌的炎症反应。
DOI：
10.18632/oncotarget.10674
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发表时间：
2018-08-10
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
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作者：
Wang BC;Lin GH;Wang B;Yan M;He B;Zhang W;Yang AK;Long ZJ;Liu Q
间变性甲状腺癌（Anaplastic thyroid cancer，ATC）是甲状腺癌的一种未分化亚型，是恶性程度最高的内分泌癌之一，生存率低，对化疗和放疗均具有抵抗性。我们发现，与正常组织和甲状腺乳头状癌（PTC）相比，UHRF 1在人ATC中高表达。UHRF 1基因的敲除抑制了ATC在体外和体内的增殖。UHRF 1过表达促进甲状腺癌细胞增殖。此外，UHRF 1抑制诱导三维（3D）培养的ATC细胞的分化，并下调去分化标志物（CD 97）的表达。同时抑制干细胞标志物（Sox 2、Oct 4和Nanog）。此外，UHRF 1基因敲低可降低ATC患者IL-8、TGF-α和TNF-α等细胞因子的转录水平，从而可能减轻ATC患者的炎症反应。本研究证实了UHRF 1在ATC增殖、去分化和炎症反应中的作用，提示UHRF 1可能成为ATC治疗的潜在靶点。
Anaplastic thyroid cancer (ATC), an undifferentiated subtype of thyroid cancer, is one of the most malignant endocrine cancer with low survival rate, and resistant to chemotherapy and radiation therapy. Here we found that UHRF1 was highly expressed in human ATC compared with normal tissue and papillary thyroid cancer (PTC). Knockdown of UHRF1 inhibited proliferation of ATC in vitro and in vivo. Consistently, overexpression of UHRF1 promoted the proliferation of thyroid cancer cells. Moreover, UHRF1 suppression induced differentiation of three-dimensional (3D) cultured ATC cells and down-regulated the expression of dedifferentiation marker (CD97). The stem cell markers (Sox2, Oct4 and Nanog) were suppressed simultaneously. In addition, UHRF1 knockdown reduced the transcription of cytokines (IL-8, TGF-α and TNF-α), which might relieve the inflammatory reaction in ATC patients. This study demonstrated a role of UHRF1 in ATC proliferation, dedifferentiation and inflammatory reaction, presenting UHRF1 as a potential target in ATC therapy.