ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
This article is part of the Research TopicLong Noncoding RNAs in CancerView all 6 articles
Pilot Study: Predicting the Interplay Between FOXO1 and its Downstream Long Non-Coding RNAs in HCC
Provisionally accepted
Rowan Abdelbary1,2
Shereine K. Saber1
Fabian Rose3
Kai Breuhahn3Shereen A. El Sobky2
Injie Fawzy2
Ahmed Moustafa1
Nada El-Ekiaby2
Ahmed Ihab Abdelaziz2*- 1The American University in Cairo, New Cairo City, Egypt
- 2New Giza University, Giza, Egypt
- 3Universitat Heidelberg, Heidelberg, Germany
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Forkhead Box O-1 (FOXO1) is one of the key regulatory transcription factors capable of regulating many critical cellular functions, such as promoting apoptosis and inhibiting cell cycle progression thereby acting as a tumor-suppressor. In hepatocellular carcinoma (HCC), FOXO1 has been shown to be downregulated in liver tissues, and the lower expression has been correlated with poor prognosis. This highlights the necessity of understanding the regulatory functions of FOXO1 in more depth. Various studies have focused on the role of non-coding RNAs (ncRNAs), mainly microRNAs, as upstream regulators of FOXO1 in HCC and how their dysregulation affects carcinogenesis. However, the role of FOXO1 as an upstream regulator of ncRNAs, specifically long non-coding RNAs (lncRNAs), remains an unexplored area of research that needs to be addressed. In this study, we aimed to dissect this interplay and to identify potential FOXO1-regulated lncRNAs which could possibly play a role in the pathogenesis of HCC. This was achieved through the analysis of publicly available ChIP-Seq data provided by ENCODE database, along with performing RNA sequencing after the knockdown of FOXO1 in Huh-7 cells. ChIP-Seq data analyses revealed a list of 982 promising lncRNAs that are possibly regulated by FOXO1. Analysis 2 of the RNA sequencing data revealed 131 lncRNAs that were differentially expressed after FOXO1 knockdown. The intersection between ChIP-Seq data and RNA sequencing data showed an overall of 12 lncRNAs that were differentially expressed upon FOXO1 knockdown and also have a FOXO1 binding site in their promoter region, namely ZFAS1, LINC00862, SNHG32, LINC01962, SNHG12, 1QCH-AS1, LINC00324, DCXR-DT, GLUD1P2, FAB5P3, JPX, and SMPD4BP. In conclusion, 12 lncRNAs were identified as potential downstream targets of FOXO1, suggesting that those lncRNAs could mediate FOXO1 functions in HCC.
Keywords: ChIP-seq, Forkhead Box O-1 (FOXO1), Hepatocellular Carcinoma, long non-coding RNA, RNA sequencing
Received: 26 Aug 2025; Accepted: 26 Jan 2026.
Copyright: © 2026 Abdelbary, Saber, Rose, Breuhahn, El Sobky, Fawzy, Moustafa, El-Ekiaby and Abdelaziz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ahmed Ihab Abdelaziz
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