Zhu Yunheng, Zhang Xiaohua, Wang Lifeng, Zhu Xiuxiang, Xia Ziyin, Xu Ling, Xu Jun
1Department of Obstetrics and Gynecology, Minhang Hospital, Fudan University, No.170 Xinsong Road, Minhang District, Shanghai, 201199 China.
Minhang District Maternal and Child Health Hospital, Shanghai, 201102 China.
Cancer Cell Int. 2020 May 6;20:152. doi: 10.1186/s12935-020-01223-w. eCollection 2020.
Previous literature has revealed long non-coding RNAs (lncRNAs) are crucial regulators for cell functions and gene expression. LncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) was reported as a biological suppressor in several types of human cancers, yet relevant mechanisms and biological effects of FENDRR with regards to cervical cancer (CC) are not explored until now.
In this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis detected gene expression in tissues and cells. Gain- or loss-of-function experiments revealed the biological effects of FENDRR and miR-15a/b-5p on CC cell functions. Bioinformatics tools were used to predict the relevant genes. Mechanism experiments including RNA immunoprecipitation (RIP) assay, pull down assay and luciferase reporter assay depicted the binding situation and coexistence of indicated genes.
FENDRR was downregulated in CC tissues and cells, which suppressed CC progression. MiR-15a-5p and miR-15b-5p shared binding sites with FENDRR and had interaction with FENDRR. Tubulin alpha1A (TUBA1A) was downregulated in CC tissues and positively modulated by FENDRR. TUBA1A was the target of miR-15a/b-5p. TUBA1A silencing rescued the effect of FENDRR overexpression on CC cell growth and migration.
FENDRR inhibits CC progression through upregulating TUBA1A in a miR-15a/b-5p-dependent manner.
既往文献表明，长链非编码RNA（lncRNA）是细胞功能和基因表达的关键调节因子。据报道，lncRNA胎儿致死性非编码发育调控RNA（FENDRR）在几种人类癌症中作为一种生物抑制因子发挥作用，但迄今为止，尚未探索FENDRR在宫颈癌（CC）中的相关机制和生物学效应。
在本研究中，采用定量实时聚合酶链反应（qRT-PCR）分析检测组织和细胞中的基因表达。功能获得或丧失实验揭示了FENDRR和miR-15a/b-5p对CC细胞功能的生物学效应。使用生物信息学工具预测相关基因。包括RNA免疫沉淀（RIP）分析、下拉分析和荧光素酶报告分析在内的机制实验描述了所示基因的结合情况和共存情况。
FENDRR在CC组织和细胞中表达下调，抑制了CC的进展。MiR-15a-5p和miR-15b-5p与FENDRR共享结合位点，并与FENDRR相互作用。微管蛋白α1A（TUBA1A）在CC组织中表达下调，并受到FENDRR的正向调节。TUBA1A是miR-15a/b-5p的靶标。TUBA1A沉默挽救了FENDRR过表达对CC细胞生长和迁移的影响。
FENDRR通过以miR-15a/b-5p依赖的方式上调TUBA1A来抑制CC进展。
