Yuan Jingwen, Lu Jiatong, Zhu Jie, Chen Fangfang, Zeng Zhi, Yan Junfeng, Li Qiang, Zhou Rui, Tong Qiang
Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Colorectal Surgery Department, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Cancer Lett. 2024 Dec 18;611:217398. doi: 10.1016/j.canlet.2024.217398.
Gastric cancer is a common global malignancy that requires detailed study of its development mechanisms. Although LncRNA FIRRE is known to play a crucial role in the progression and treatment resistance of several cancers, its effect on gastric cancer is not well understood. This study confirms the impact of FIRRE on the malignant behavior of gastric cancer. Using RNA-sequencing, dual luciferase reporter assay, RIP and CHIP, we identified transcription factors and target genes linked to FIRRE. Elevated FIRRE expression in gastric cancer correlates with worse patient prognosis and promotes gastric cancer proliferation, migration, and invasion both in vitro and in vivo. FIRRE regulates the TUBB3 gene, facilitating gastric cancer progression by activating the TUBB3 promoter in vitro. ZFP64 is the transcription factor for TUBB3, activating its promoter and binding specifically with FIRRE. Reducing ZFP64 disrupts FIRRE's positive regulation of TUBB3 in vitro and in vivo. This study shows FIRRE promotes gastric cancer progression by binding to ZFP64 and activating the TUBB3 promoter.
胃癌是一种常见的全球恶性肿瘤,需要对其发生机制进行详细研究。尽管已知长链非编码RNA FIRRE在多种癌症的进展和治疗耐药性中起关键作用,但其对胃癌的影响尚不清楚。本研究证实了FIRRE对胃癌恶性行为的影响。通过RNA测序、双荧光素酶报告基因检测、RNA免疫沉淀和染色质免疫沉淀,我们确定了与FIRRE相关的转录因子和靶基因。胃癌中FIRRE表达升高与患者预后较差相关,并在体外和体内促进胃癌的增殖、迁移和侵袭。FIRRE通过在体外激活TUBB3启动子来调节TUBB3基因,从而促进胃癌进展。ZFP64是TUBB3的转录因子,可激活其启动子并与FIRRE特异性结合。在体外和体内降低ZFP64会破坏FIRRE对TUBB3的正向调节。本研究表明,FIRRE通过与ZFP64结合并激活TUBB3启动子来促进胃癌进展。