Wentao Huang1, Hongjing Liu2, Tianzhu Lv3. 1. Savaid Stomatology School, Hangzhou Medical College, Hangzhou, Zhejiang, China. 2. College of Stomatology of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, China. 3. College of Stomatology of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, China. ltz_0628@126.com.
Abstract
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most comment types of oral malignancies. SET-domain-containing protein 6 (SETD6) was recently identified as an important regulator of multiple signaling pathways through methylating protein substrates. Meanwhile, SETD6 is known to participate in multiple cancers. However, the role of SETD6 in OSCC remains unclear. METHODS: Gene and protein expressions in OSCC cells or tissues were detected by RT-qPCR and western blot, respectively. In addition, CCK-8 assay was used to test the cell viability. A transwell assay was performed to measure cell migration and invasion. Flow cytometry was used to test cell apoptosis and cycle. Meanwhile, methylation-specific PCR (MSP) was used to detect the status of promoter methylation. RESULTS: SETD6 was significantly upregulated in OSCC tissues. In addition, knockdown of SETD6 notably inhibited the proliferation and induced the apoptosis of OSCC cells. Furthermore, silencing of SETD6 notably suppressed the migration and invasion of OSCC cells. Meanwhile, SETD6 siRNA significantly inhibited the promoter methylation of RelA (NF-κB p65) and PAK4. Furthermore, SETD6 siRNA induced G1 arrest in OSCC cells. CONCLUSION: Knockdown of SETD6 inhibits the tumorigenesis of OSCC by suppressing promoter methylation of PAK4 and RelA. Therefore, our study might shed new light on exploring strategies for the treatment of OSCC.
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most comment types of oral malignancies. SET-domain-containing protein 6 (SETD6) was recently identified as an important regulator of multiple signaling pathways through methylating protein substrates. Meanwhile, SETD6 is known to participate in multiple cancers. However, the role of SETD6 in OSCC remains unclear. METHODS: Gene and protein expressions in OSCC cells or tissues were detected by RT-qPCR and western blot, respectively. In addition, CCK-8 assay was used to test the cell viability. A transwell assay was performed to measure cell migration and invasion. Flow cytometry was used to test cell apoptosis and cycle. Meanwhile, methylation-specific PCR (MSP) was used to detect the status of promoter methylation. RESULTS: SETD6 was significantly upregulated in OSCC tissues. In addition, knockdown of SETD6 notably inhibited the proliferation and induced the apoptosis of OSCC cells. Furthermore, silencing of SETD6 notably suppressed the migration and invasion of OSCC cells. Meanwhile, SETD6 siRNA significantly inhibited the promoter methylation of RelA (NF-κB p65) and PAK4. Furthermore, SETD6 siRNA induced G1 arrest in OSCC cells. CONCLUSION: Knockdown of SETD6 inhibits the tumorigenesis of OSCC by suppressing promoter methylation of PAK4 and RelA. Therefore, our study might shed new light on exploring strategies for the treatment of OSCC.
Authors: Dan Levy; Alex J Kuo; Yanqi Chang; Uwe Schaefer; Christopher Kitson; Peggie Cheung; Alexsandra Espejo; Barry M Zee; Chih Long Liu; Stephanie Tangsombatvisit; Ruth I Tennen; Andrew Y Kuo; Song Tanjing; Regina Cheung; Katrin F Chua; Paul J Utz; Xiaobing Shi; Rab K Prinjha; Kevin Lee; Benjamin A Garcia; Mark T Bedford; Alexander Tarakhovsky; Xiaodong Cheng; Or Gozani Journal: Nat Immunol Date: 2010-12-05 Impact factor: 25.606
Authors: Lee Admoni-Elisha; Tzofit Elbaz; Anand Chopra; Guy Shapira; Mark T Bedford; Christopher J Fry; Noam Shomron; Kyle Biggar; Michal Feldman; Dan Levy Journal: Nucleic Acids Res Date: 2022-06-13 Impact factor: 19.160