Forkhead box K1 facilitates growth of papillary thyroid carcinoma cells by regulating connective tissue growth factor ex
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RESEARCH ARTICLE
Forkhead box K1 facilitates growth of papillary thyroid carcinoma cells by regulating connective tissue growth factor expression Hongwei Xu1 · Yang Liu1 · Zheng Liu1 · Xiaoming Wang1 · Xiubo Lu1 Received: 30 June 2020 / Accepted: 11 October 2020 © Japan Human Cell Society 2020
Abstract Forkhead box (FOX) proteins have been identified as key transcription factors in diverse biological processes involved in tumor progression. A large number of FOX proteins are implicated in tumorigenesis of papillary thyroid carcinoma (PTC). Here we investigated the role of Forkhead box K1 (FOXK1) in PTC progression. First, we found that FOXK1 was elevated in both PTC tissues (N = 68) and cell lines. Moreover, up-regulated FOXK1 was associated with shorter overall survival of PTC patients. Second, in vitro functional assays showed that FOXK1 promoted progression of PTC. Mechanistically, FOXK1 could bind to the promoter of cysteine-rich angiogenic inducer 61 (CYR61) and regulate connective tissue growth factor (CTGF) expression through CYR61. Notably, over-expression of CTGF weakened suppression of PTC progression induced by FOXK1 knockdown. Finally, in vivo xenotransplant tumor model indicated that knockdown of FOXK1 suppressed PTC growth. In conclusion, our results indicate that FOXK1 exerts oncogenic roles in PTC via CYR61/CTGF axis, which suggests FOXK1 might act as a potential therapeutic target. Keywords FOXK1 · CYR61 · CTGF · PTC · Progression
Introduction Thyroid cancer is the most common malignant tumor of the endocrine system, accounting for 5–10% of cancers in female [1]. Among various histological subtypes of thyroid cancer, papillary thyroid carcinoma (PTC) accounts for 80% [2]. Although PTC is a relatively inert disease with low mortality, 20% of PTC patients have certain clinical and pathological characteristics, including older diagnosis age, larger tumor volume, lymph node metastasis, and poor prognosis [3]. Thus, it is particularly important to discover novel therapeutic targets for PTC through investigation of molecular mechanisms involved in PTC progression. Forkhead box (FOX) proteins, with common DNAbinding domain [4], function as transcriptional regulators Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00450-7) contains supplementary material, which is available to authorized users. * Xiubo Lu [email protected] 1
Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, Longhu Middle Ring Road, Jinshui District, Zhengzhou 450052, Henan, China
in various biological processes, such as metabolism, proliferation, migration and invasion [5]. Recently, FOX proteins have been found to be associated with different hallmarks of cancer, including tumor invasion and metastasis, cell death and tumor promoting inflammation [6]. Dysregulation of FOX proteins contributes to tumorigenesis and cancer progression [7], especially in PTC. For example, FOXP3 is abnormally expressed in PTC [8], and highly express
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