Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
Anticancer Res. 2020 May;40(5):2645-2655. doi: 10.21873/anticanres.14235.
BACKGROUND/AIM: Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells.
Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system.
MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G/M phase, DNA damage and apoptotic cell death.
MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G/M cell cycle arrest resulting in DNA damage and apoptosis.
背景/目的：三分之二的头颈部鳞状细胞癌（HNSCC）患者表现为局部晚期（LA）阶段，生存率较低。本研究旨在探讨长链非编码 RNA MALAT1 对 HNSCC 细胞放射和顺铂敏感性的作用。
采用 CRISPR/Cas9 系统敲低 MALAT1 后，通过集落形成、细胞活力和细胞凋亡实验检测细胞的放射敏感性和顺铂敏感性。
与非致瘤细胞系相比，MALAT1 在 HNSCC 细胞系中过表达。敲低 MALAT1 后，经放射处理后形成的菌落数量明显减少。MALAT1 敲低组细胞的顺铂 IC 值低于对照组细胞。MALAT1 敲低导致细胞周期停滞在 G/M 期，引发 DNA 损伤和凋亡性细胞死亡。
MALAT1 敲低通过诱导 G/M 细胞周期停滞导致 DNA 损伤和凋亡，增强了 HNSCC 细胞对放射和顺铂的敏感性。
