Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway;
Anticancer Res. 2020 Dec;40(12):6677-6684. doi: 10.21873/anticanres.14691.
To analyze the biological role of the long non-coding RNA LINK-A.
An 850-bp segment from the second exon of LINK-A was removed using the CRISPR/Cas9 system in OVCA433 ovarian serous carcinoma cells. Spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity and expression of cell-signaling proteins were assessed in vitro.
OVCA433 cells with LINK-A deletion were more invasive (p=0.0008) but had reduced migration and MMP9 secretion compared to controls (p=0.003 and p=0.005, respectively). LINK-A deletion did not affect proliferation but induced phosphorylation of extracellular signal-regulated kinase (10-fold; p=0.005). LINK-A knock out additionally reduced spheroid formation.
Added to our previous data from analysis of clinical specimens, LINK-A is likely to be a tumor suppressor.
分析长链非编码 RNA LINK-A 的生物学功能。
利用 CRISPR/Cas9 系统从 LINK-A 的第二个外显子中切除 850bp 片段,在卵巢浆液性癌细胞系 OVCA433 中进行研究。体外评估球体形成、迁移、侵袭、增殖、基质金属蛋白酶(MMP)活性和细胞信号蛋白的表达。
与对照组相比,LINK-A 缺失的 OVCA433 细胞侵袭性更强(p=0.0008),但迁移和 MMP9 分泌减少(p=0.003 和 p=0.005)。LINK-A 缺失不影响增殖,但诱导细胞外信号调节激酶磷酸化(增加 10 倍;p=0.005)。LINK-A 敲除还减少了球体形成。
结合我们之前对临床标本的分析数据,LINK-A 可能是一种肿瘤抑制因子。