Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Mol Carcinog. 2023 Jul;62(7):920-939. doi: 10.1002/mc.23535. Epub 2023 Apr 4.
Arecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline-induced oral cancer and further verify their expressions and roles.
This study included a data-mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels.
MYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline-transformed oral cells and oral cancer cells.
This study revealed MYO1B as a key gene in Arecoline-induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.
槟榔中的主要成分槟榔碱通过复杂而不明确的机制诱导口腔细胞恶性转化。因此，我们旨在筛选参与槟榔碱诱导口腔癌的关键基因，并进一步验证它们的表达和作用。
本研究包括数据挖掘部分、生物信息学验证部分和实验验证部分。首先，筛选与槟榔碱诱导的口腔癌相关的关键基因。然后，验证关键基因在头颈部/口腔癌组织中的表达和临床意义，并探讨其下游作用机制。随后，通过组织学和细胞学水平的实验验证关键基因的表达和作用。
肌球蛋白 1B（MYO1B）被鉴定为关键基因。MYO1B 的过表达与口腔癌的淋巴结转移和不良预后相关。MYO1B 可能主要与转移、血管生成、缺氧和分化有关。MYO1B 与巨噬细胞、B 细胞和树突状细胞的浸润呈正相关。MYO1B 可能与 SMAD3 密切相关，SMAD3 可能富集在 Wnt 信号通路中。抑制 MYO1B 显著抑制了槟榔碱转化的口腔细胞和口腔癌细胞的增殖、侵袭和转移能力。
本研究揭示了 MYO1B 是槟榔碱诱导口腔肿瘤发生的关键基因。MYO1B 可能是口腔癌的一个新的预后指标和治疗靶点。
