MOF Regulates TNK2 Transcription Expression to Promote Cell Proliferation in Thyroid Cancer.

Danyang Li,Danyang Li,Mingxiao Duan,Xiangzhi Li,Bo Chen,Shuang Gao,Meng Wang,Xinghong Guo,Xinghong Guo

doi:10.3389/fphar.2020.607605

Abstract

MOF is a well-known histone acetyltransferase to catalyze acetylation of histone H4 lysine 16 (K16), and it is relevant to diverse biological processes, such as gene transcription, cell cycle, early embryonic development and tumorigenesis. Here, we identify MOF as an oncogene in most thyroid cancer. It is found that expression level of MOF was significantly upregulated in most thyroid cancer tissue samples and cell lines. MOF-deficient in both BHP-10-3 and TT2609 cell lines inhibited cell proliferation by blocking the cell cycle in G1 phase and enhanced cell apoptosis. Mechanistically, MOF bound the TNK2 promoter to activate TNK2 transcription. Furthermore, the expression level of TNK2 was decreased with the histone acetyltransferase inhibitor. Besides, MOF promoted proliferation of thyroid cancer cells through increased phosphorylation of AKT, thus activating the PI3K/AKT pathway. Ultimately, our findings indicated that MOF played an oncogene role in development and progression of thyroid cancer and may be a potential novel target for the treatment of thyroid cancer.

Highlights

Thyroid cancer is the most common malignant tumor of the head and neck with high morbidity
Our study found that histone acetyltransferase MOF is up-regulated in most thyroid cancers, revealing that MOF plays an important role in the proliferation and apoptosis of thyroid cancer cells
This effect is based on the direct transcriptional activation of TNK2 by MOF and change of downstream PI3K/AKT signaling pathway

Summary

Introduction

Thyroid cancer is the most common malignant tumor of the head and neck with high morbidity. According to the statistics of the National Cancer Center in 2018, thyroid cancer has become the fourth most malignant tumor in women. Molecular targeted therapy is of great significance. Current research confirms that some genetic mutations occur in up to 97% thyroid cancer (Cancer Genome Atlas Research Network, 2014). Most thyroid cancers are closely related to MAPK, VEGF, and PI3K signaling pathways, while BRAF, RAS and RET genes have higher mutation rates, which provides molecular targets for thyroid cancer (Thomas et al, 2014). Six molecular targets of thyroid cancer including BRAF, RET, NTRK1, G-GAS, K-RAS, and N-RAS have already been reported (Xing, 2013). Though BRAF inhibitor sorafenib has been used clinically, others are still in the basic research or clinical trial phase (Thomas et al, 2014)

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