Long Non-coding RNA FENDRR Acts as a miR-423-5p Sponge to Suppress the Treg-Mediated Immune Escape of Hepatocellular Carcinoma Cells

Abstract

Long non-coding RNAs (lncRNAs) have been known to partake in the development and the immune escape of hepatocellular carcinoma (HCC). The initial microarray analysis of GSE115018 expression profile revealed differentially expressed lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) in HCC. Therefore, this study’s main purpose was to explore the mechanism of tumor suppressor lncRNA FENDRR in regulating the immune escape of HCC cells. Notably, it was further validated through this study that lncRNA FENDRR competitively bound to microRNA-423-5p (miR-423-5p), and miR-423-5p specifically targeted growth arrest and DNA-damage-inducible beta protein (GADD45B). The effects that lncRNA FENDRR and miR-423-5p have on the cell proliferation and apoptosis, the immune capacity of regulatory T cells (Tregs), and the tumorigenicity of HCC cells were examined through overexpressing or the knocking down of lncRNA FENDRR and miR-423-5p both in vitro and in vivo . Subsequently, lncRNA FENDRR and GADD45B were revealed to have poor expressions in HCC. Meanwhile, miR-423-5p was highly expressed in HCC. Importantly, overexpressed lncRNA FENDRR and downregulated miR-423-5p diminished cell proliferation and tumorigenicity, and promoted apoptosis in HCC cells, thus regulating the immune escape of HCC mediated by Tregs. Taken conjointly, lncRNA FENDRR inhibited the Treg-mediated immune escape of HCC cells by upregulating GADD45B by sponging miR-423-5p.

LncRNA BCYRN1/miR-490-3p/POU3F2, served as a ceRNA network, is connected with worse survival rate of hepatocellular carcinoma patients and promotes tumor cell growth and metastasis

“…It has been well demonstrated that several lncRNAs played vital roles in the modulation of HCC cells growth, invasion, and migration [27,28]. For example, BCYRN1 has been identified to promote tumor growth and regulate metastasis in some cancers, such as non-small-cell lung cancer, colorectal cancer and so on [7,8].…”

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

“…Microarray analysis suggested that the expression of FENDRR lncRNA in HCC samples was higher than that in the normal samples. Recent studies also suggested that FENDRR lncRNA suppressed the immune escape of HCC cells (61). The HCC cells transfected with siRNA of FENDRR lncRNA exhibited increased expression of TGF-β, IL-10, and VEGF.…”

Construction of circRNA-based ceRNA Network to Reveal the Role of circRNAs in the Progression and Prognosis of Hepatocellular Carcinoma

“…Non-coding RNA (ncRNA), including lnc RNA, microRN and circRNA, is transcribed from the genome without being translated into protein. NcRNA can control gene expression at various levels, including epigenetic modi cation [14,15], transcription [15], RNA splicing [16,17], scaffold assembly [17], etc. CircRNAs has tissue-speci c expression pattern and has potential to be biomarker, so it could be used as clinical diagnosis and prognostic indicators.…”