Ma Jia, Zhao Gang, Du Jia, Li Jiang, Lin Guangshuai, Zhang Jianfei
Department of Surgical Oncology, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, People's Republic of China.
Department of Surgical Oncology, Pucheng County Hospital, Weinan, 715500, Shaanxi, People's Republic of China.
Cancer Manag Res. 2021 Dec 14;13:9175-9187. doi: 10.2147/CMAR.S329419. eCollection 2021.
This study aimed to investigate the regulatory effect of lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) on gastric cancer (GC) progression.
The expression levels of FENDRR in GC tissues and paracancerous tissues, as well as in gastric normal epithelial cell line and GC cell lines were detected. The Ad-FENDRR or si-FENDRR was transfected into AGS and SGC-7901 cells, and cell proliferation, invasion and apoptosis were determined. Online bioinformatics database predicted and screened miR-421 as a potential target of FENDRR, and SIRT3 was predicted as a target gene of miR-421. The pcDNA-SIRT3 or si-SIRT3 was transfected into AGS cells, and cell proliferation, invasion, apoptosis and Notch-1 protein expression were determined. Ad-FENDRR was transfected into AGS and SGC-7901 cells alone or together with miR-421 mimic to explore the effect of miR-421 on cells. The AGS cells transfected with Ad-FENDRR were injected into the armpits of nude mice to establish subcutaneous xenograft tumor model, and tumor growth was observed.
FENDRR expression was downregulated in GC tissues and cell lines. Overexpression of FENDRR or SIRT3 inhibited tumor proliferation and invasion, and promoted apoptosis. The overexpression of Notch-1 reversed the inhibitory effect of SIRT3 on AGS cell. MiR-421 mimic reversed the inhibitory effect of FENDRR on the growth of AGS and SGC-7901 cells. Nude mice injected with FENDRR overexpressing AGS cells had smaller tumor volume and weight and weaker tumor cell proliferation ability.
FENDRR inhibits Notch-1 pathway to inhibit GC cell proliferation and invasion by upregulating SIRT3 expression via targeting miR-421.
本研究旨在探讨长链非编码RNA胎儿致死性非编码发育调控RNA（FENDRR）对胃癌（GC）进展的调控作用。
检测FENDRR在GC组织和癌旁组织以及胃正常上皮细胞系和GC细胞系中的表达水平。将Ad-FENDRR或si-FENDRR转染至AGS和SGC-7901细胞中，检测细胞增殖、侵袭和凋亡情况。在线生物信息学数据库预测并筛选出miR-421作为FENDRR的潜在靶标，SIRT3被预测为miR-421的靶基因。将pcDNA-SIRT3或si-SIRT3转染至AGS细胞中，检测细胞增殖、侵袭、凋亡及Notch-1蛋白表达情况。单独或与miR-421模拟物一起将Ad-FENDRR转染至AGS和SGC-7901细胞中，探讨miR-421对细胞的影响。将转染Ad-FENDRR的AGS细胞注射到裸鼠腋窝建立皮下异种移植瘤模型，观察肿瘤生长情况。
FENDRR在GC组织和细胞系中表达下调。FENDRR或SIRT3过表达抑制肿瘤增殖和侵袭，并促进凋亡。Notch-1过表达逆转了SIRT3对AGS细胞的抑制作用。miR-421模拟物逆转了FENDRR对AGS和SGC-7901细胞生长的抑制作用。注射过表达FENDRR的AGS细胞的裸鼠肿瘤体积和重量较小，肿瘤细胞增殖能力较弱。
FENDRR通过靶向miR-421上调SIRT3表达，抑制Notch-1通路，从而抑制GC细胞增殖和侵袭。
