Abstract
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.
Highlights
Anaplastic thyroid cancer (ATC) has a poor prognosis with only half a year survival lifespan after diagnosis [1, 2]
In order to study the role of UHRF1 in thyroid cancer, especially the ATC, we searched the public data in NCBI (GEO) and selected two microarray chips, GSE9115 [29], which contained 4 normal thyroid tissues, 9 papillary thyroid cancer (PTC) and 5 ATC samples, and GSE33630 [30, 31], which contained 45 normal thyroid tissues, 49 PTC and 11 ATC samples
We found that ATC did not show the regular structure of normal thyroid follicle and the nest cancer cells exhibited strong staining for UHRF1, compared with paracarcinoma tissue and PTC
Summary
Anaplastic thyroid cancer (ATC) has a poor prognosis with only half a year survival lifespan after diagnosis [1, 2]. ATC exhibits faster growth properties in comparison with well-differentiated thyroid cancer. Surgery and chemo-/radio-therapies are not effective in ATC [3,4,5,6]. ATC is known as an undifferentiated thyroid cancer. ATC loses the normal thyroid ability, including the ability to express the thyroid stimulating hormone (TSH) receptor, leading to the resistance to TSH suppressive treatment. Differentiation therapy in ATC aims to regain the thyroid-specific structure and function. ATRA and histone deacetylase inhibitors (HDAC inhibitors) provide a differentiation therapy option for ATC. The effectiveness of these drugs for ATC patients is limited [7, 8]. Additional therapies are needed and identifying novel molecular targets underlying ATC tumorigenesis is crucial for the development of ATC therapy
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