Department of Stomatology, Qingdao Municipal Hospital, Qingdao 266071, People's Republic of China; Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.
Department of Stomatology, People's Hospital of Qingdao Huangdao District, Qingdao 266400, People's Republic of China.
Arch Oral Biol. 2022 Feb;134:105320. doi: 10.1016/j.archoralbio.2021.105320. Epub 2021 Nov 24.
This research investigated the biological role of isoprenylcysteine carboxyl methyltransferase (ICMT) in tongue squamous cell carcinoma (TSCC) progression meanwhile to explore the conceivable mechanism.
The mRNA and protein expression were measured using real-time PCR and Western blot. Cell proliferation, apoptosis, cycle distribution, migration and invasion were evaluated by CCK-8 assay, flow cytometry, wound-healing assay and transwell assay. The anti-tumor activity of ICMT silencing was observed in nude mice.
Our results indicated that silencing of ICMT-mediated methylation effectively inhibited TSCC cells proliferation in vitro and reduced tumor growth in vivo. Moreover, ICMT knockdown also induced cell apoptosis and cell cycle arrest of both CAL-27 and SCC-4 cells. In addition, CAL-27 and SCC-4 cells migration and invasion were weakened by ICMT siRNA. Mechanistically, ICMT deficiency significantly decreased the K-Ras and RhoA membrane targeting localization, leading to the suppression of K-Ras- and RhoA-mediated downstream signaling in CAL-27 and SCC-4 cells.
Altogether, our findings identified a crucial role played by ICMT in the progression of TSCC and the potential mechanisms by which exerted its effects, indicating that targeting ICMT may represent a promising therapeutic strategy for TSCC.
本研究旨在探讨异戊烯基半胱氨酸羧基甲基转移酶（ICMT）在舌鳞癌（TSCC）进展中的生物学作用，并探讨其可能的机制。
采用实时 PCR 和 Western blot 检测 mRNA 和蛋白表达。通过 CCK-8 测定、流式细胞术、划痕愈合试验和 Transwell 试验评估细胞增殖、凋亡、细胞周期分布、迁移和侵袭。在裸鼠中观察 ICMT 沉默的抗肿瘤活性。
研究结果表明，ICMT 介导的甲基化沉默有效抑制了 TSCC 细胞的体外增殖，并降低了体内肿瘤生长。此外，ICMT 敲低还诱导了 CAL-27 和 SCC-4 细胞的细胞凋亡和细胞周期停滞。此外，ICMT siRNA 削弱了 CAL-27 和 SCC-4 细胞的迁移和侵袭。机制上，ICMT 缺失显著降低了 K-Ras 和 RhoA 的膜定位，从而抑制了 CAL-27 和 SCC-4 细胞中 K-Ras 和 RhoA 介导的下游信号转导。
总之，我们的研究结果确定了 ICMT 在 TSCC 进展中的重要作用及其发挥作用的潜在机制，表明靶向 ICMT 可能代表治疗 TSCC 的一种有前途的治疗策略。
