Zhang Nan, Zeng Lingfang, Wang Shouyi, Wang Ronghua, Yang Rui, Jin Zuolin, Tao Hong
Department of Stomatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xian, Shanxi, 710061, People's Republic of China.
Department of Pediatric Stomatology, Jinan Stomatological Hospital, Jinan, Shandong, 250000, People's Republic of China.
Onco Targets Ther. 2021 Feb 4;14:795-806. doi: 10.2147/OTT.S277351. eCollection 2021.
Oral squamous cell carcinoma (OSCC) is a common cancer especially young people in the world. The long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to be closely associated with the progression of various human cancers. However, the role of FER1L4 in OSCC remains unclear.
The expression level of FER1L4 in OSCC tissues and cancer cell lines was detected by using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and EdU staining assay. Cell invasion and migration were evaluated by Transwell assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was performed to determine the targeting relationship between FER1L4, miR-133a-5p and Prx1. The protein expression of Prx1 was detected by Western blot. In addition, a xenograft tumor model in vivo was constructed to confirm the function of FER1L4.
FERIL4 was significantly upregulated in OSCC tissues and cancer cell lines. Moreover, high level of FER1L4 predicted a poor prognosis of OSCC patients. Silencing of FER1L4 not only significantly inhibited cell growth, invasion, migration and induced apoptosis in SCC-9 and HN4 cells in vitro, but also effectively suppressed the tumorigenesis of OSCC cells in vivo. Knockdown of FER1L4 significantly enhanced the expression of miR-133a-5p by sponging it, and then downregulated Prx1 expression.
Our study elucidated a new mechanism of lncRNA FER1L4 that promoting OSCC progression by directly targeting miR-133a-5p/Prx1 axis and provided novel therapeutic targets for OSCC.
口腔鳞状细胞癌（OSCC）是一种常见癌症，在全球尤其是年轻人中较为普遍。据报道，长链非编码RNA Fer-1样蛋白4（FER1L4）与多种人类癌症的进展密切相关。然而，FER1L4在OSCC中的作用仍不清楚。
采用定量实时聚合酶链反应（qRT-PCR）检测OSCC组织和癌细胞系中FER1L4的表达水平。通过细胞计数试剂盒-8（CCK-8）检测和EdU染色检测评估细胞增殖。通过Transwell检测评估细胞侵袭和迁移。通过流式细胞术检测细胞凋亡。进行荧光素酶报告基因检测以确定FER1L4、miR-133a-5p和Prx1之间的靶向关系。通过蛋白质免疫印迹法检测Prx1的蛋白表达。此外，构建体内异种移植肿瘤模型以证实FER1L4的功能。
FERIL4在OSCC组织和癌细胞系中显著上调。此外，FER1L4水平高预示着OSCC患者预后不良。沉默FER1L4不仅在体外显著抑制SCC-9和HN4细胞的生长、侵袭、迁移并诱导凋亡，而且在体内有效抑制OSCC细胞的肿瘤发生。敲低FER1L4通过海绵吸附作用显著增强miR-133a-5p的表达，进而下调Prx1表达。
我们的研究阐明了lncRNA FER1L4通过直接靶向miR-133a-5p/Prx1轴促进OSCC进展的新机制，并为OSCC提供了新的治疗靶点。
