Abstract
Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence, has a strong propensity for neck lymph node metastasis. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Tripartite motif protein 29 (TRIM29) is dysregulated in various cancer and functions as oncogene or tumor suppressor in discrete cancers. In this study, we found that both TRIM29 and fibronectin 1 (FN1) were upregulated with positive correlation in PTC tissues. Neither overexpression nor downregulation of TRIM29 altered the proliferation of PTC cells significantly. Overexpression of TRIM29 significantly promotes, while knockdown of TRIM29 significantly decreases migration and invasion by regulating FN1 expression in PTC cells. In terms of mechanism, we found that TRIM29 altered the stability of FN1 mRNA via regulation of miR-873-5p expression. The current study also demonstrated that long non-coding RNA (LncRNA) CYTOR suppressed maturation of miR-873-5p via interaction with premiR-873, and TRIM29 decreased miR-873-5p via upregulation of CYTOR. This study suggests that involvement of TRIM29 in migration and invasion in PTC cells may reveal potential metastatic mechanism of PTC and represent a novel therapeutic target and strategy.
Highlights
Thyroid cancer (TC) is the most frequent endocrine cancer, the appreciable rising incidence rates have been reported globally across multiple epidemiologic studies over the last few decades[1,2,3]
Despite Tripartite motif protein 29 (TRIM29) plays both promotive and suppressive roles in different cancers, a previous study reported that TRIM29 was upregulated and correlated with poor prognosis in TC patients, and functions as a oncogene via P13K/AKT signaling pathway[24], another study observed that TRIM29 regulated cell growth via long non-coding RNA (LncRNA) HOXA11-AS/miR-761/TRIM29 axis[25]
TRIM29 encodes for a member of the tripartite motif (TRIM) protein family, which generally function as E3 ubiquitin ligases as they contain a RING-finger domain[34]
Summary
Thyroid cancer (TC) is the most frequent endocrine cancer, the appreciable rising incidence rates have been reported globally across multiple epidemiologic studies over the last few decades[1,2,3]. It is already the sixth most common cancer among women in the United States[4]. Despite TRIM29 plays both promotive and suppressive roles in different cancers, a previous study reported that TRIM29 was upregulated and correlated with poor prognosis in TC patients, and functions as a oncogene via P13K/AKT signaling pathway[24], another study observed that TRIM29 regulated cell growth via LncRNA HOXA11-AS/miR-761/TRIM29 axis[25]. Considering that TRIM29 is a unique multifunctional TRIM protein involved in many other signaling pathways such as Wnt/ beta-catenin and TWIST, it is necessary to further verify other biological function and molecular mechanism especially in PTC
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