Xu Gang, Zhang Yan, Li Na, Wu Yanling, Zhang Jinbiao, Xu Rui, Ming Hui
Oncology Department, The 960th Hospital of the PLA, No. 20 Zhanbei Road, Zibo, 255300 Shandong China.
Cancer Cell Int. 2020 Apr 26;20:136. doi: 10.1186/s12935-020-01207-w. eCollection 2020.
The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle.
RT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes.
LBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression.
In a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.
长链非编码RNA(lncRNA)在人类癌症中的关键作用已得到证实。表达异常的lncRNA在肿瘤进展中可作为肿瘤抑制因子或癌基因。曾有报道称LBX2-AS1可促进食管鳞状细胞癌。然而,其在胃癌(GC)中的功能仍是个谜。
采用RT-qPCR检测GC细胞系中NFIC/LBX2-AS1/miR-491-5p/ZNF703的表达。通过集落形成、EdU、流式细胞术分析、Transwell和伤口愈合试验评估LBX2-AS1在GC中的功能。利用荧光素酶报告基因、染色质免疫沉淀和RNA下拉试验评估基因之间的相互作用。
LBX2-AS1在GC细胞系中上调。敲低LBX2-AS1可抑制GC细胞的增殖、迁移和侵袭能力。此外,LBX2-AS1受NFIC转录激活。并且LBX2-AS1可与miR-491-5p结合。此外,miR-491-5p缺失或ZNF703上调可抵消LBX2-AS1沉默对GC进展的抑制作用。
总之,由NFIC上调的LBX2-AS1通过靶向miR-491-5p/ZNF703促进GC进展,这意味着LBX2-AS1是GC患者潜在的治疗靶点。