Isoprenylcysteine carboxyl methyltransferase promotes the progression of tongue squamous cell carcinoma via the K-Ras and RhoA signaling pathways. (February 2022)

• Record Type: Journal Article
• Authors: Wang, Shaoru; Wang, Wei; Zhang, Shengchao; Yang, Fang; Qiu, Jing; Guo, Qingyuan; Zheng, Jiawei; Chen, Zhenggang
• Is Part Of: Archives of oral biology. Volume 134(2022)
• Publication Date: 2022-02
• Subjects: ICMT isoprenylcysteine carboxyl methyltransferase -- TSCC tongue squamous cell carcinoma -- CCK-8 Cell Counting Kit-8 -- siRNA small interfering RNA -- MMP-2 matrix metalloproteinase-2 -- MMP-9 matrix metalloproteinase-9; Isoprenylcysteine carboxyl methyltransferase -- Tongue squamous cell carcinoma -- K-Ras -- RhoA; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2021.105320
• Languages: English
• ISSNs: 0003-9969

Abstract

Abstract: Objective: This research investigated the biological role of isoprenylcysteine carboxyl methyltransferase (ICMT) in tongue squamous cell carcinoma (TSCC) progression meanwhile to explore the conceivable mechanism. Methods: 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. Results: 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. Conclusions: 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. Highlights: ICMT silencing inhibits growth and promotes apoptosis in TSCC cells. ICMT silencing induces cell cycle arrest in TSCC cells. ICMT silencing suppresses migration and invasion in TSCC cells. ICMT silencing downregulates the K-Ras and RhoA signaling pathways. ICMT knockdown reduces tumor growth in vivo.