Tang Dongxiao, Cao Congyuan, Li Wuguo, Wang Anxun
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, China.
Department of Stomatology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510630, China.
BMC Cancer. 2024 Dec 3;24(1):1489. doi: 10.1186/s12885-024-13253-y.
Head and neck squamous cell carcinoma (HNSCC) has been recognized as the seventh most prevalent malignant tumor globally. It is a malignant neoplasm that arises from the mucosal epithelium of head and neck region. In our previous research, we have demonstrated that MTUS1/ATIP1 exhibits anti-cancer properties in HNSCC. Nevertheless, the underlying mechanism responsible for the reduction of MTUS1/ATIP1 expression has not been investigated.
HNSCC and adjacent normal tissues were collected and examined using mA MeRIP-seq, qRT-PCR, and IHC to investigate the relationship between MTUS1/ATIP1 and FTO. MeRIP-qPCR, mA dot blot, RNA and protein stability assays, and RNC-qRT-PCR were employed to elucidate the mechanism by which FTO mediates demethylation of MTUS1/ATIP1 in HNSCC. Functional assays, subcutaneous tumorigenesis, and in situ tongue cancer models were conducted to assess the impact of the FTO-MTUS1/ATIP1 pathway on proliferative capacity of HNSCC tumors.
FTO was observed to be markedly upregulated and showed a negative correlation with MTUS1/ATIP1 expression in HNSCC. FTO was responsible for mediating mA demethylation in the 3'UTR of MTUS1/ATIP1, leading to its degradation. Additionally, silencing MTUS1/ATIP1 successfully reversed the tumor-promoting effects on HNSCC triggered by FTO in in vitro and in vivo.
Our research elucidated the functional importance of FTO-mediated mA demethylation of MTUS1/ATIP1, suggesting that targeting the FTO-MTUS1/ATIP1 axis could be a prospective novel approach for treating HNSCC.
头颈部鳞状细胞癌（HNSCC）已被公认为全球第七大常见恶性肿瘤。它是一种起源于头颈部区域黏膜上皮的恶性肿瘤。在我们之前的研究中，我们已经证明MTUS1/ATIP1在HNSCC中具有抗癌特性。然而，MTUS1/ATIP1表达降低的潜在机制尚未得到研究。
收集HNSCC组织和相邻正常组织，采用mA MeRIP-seq、qRT-PCR和免疫组化（IHC）检测MTUS1/ATIP1与FTO之间的关系。采用MeRIP-qPCR、mA斑点印迹、RNA和蛋白质稳定性测定以及RNC-qRT-PCR来阐明FTO介导HNSCC中MTUS1/ATIP1去甲基化的机制。进行功能测定、皮下肿瘤发生和原位舌癌模型，以评估FTO-MTUS1/ATIP1通路对HNSCC肿瘤增殖能力的影响。
在HNSCC中观察到FTO明显上调，并且与MTUS1/ATIP1表达呈负相关。FTO负责介导MTUS1/ATIP1 3'UTR中的mA去甲基化，导致其降解。此外，在体外和体内沉默MTUS1/ATIP1成功逆转了FTO对HNSCC的促肿瘤作用。
我们的研究阐明了FTO介导的MTUS1/ATIP1 mA去甲基化的功能重要性，表明靶向FTO-MTUS1/ATIP1轴可能是治疗HNSCC的一种有前景的新方法。
