Hypoxia-driven LncRNA CTD-2510F5.4: a Potential Player in Hepatocellular Carcinoma's Prognostic Stratification, Cellular Behavior, Tumor Microenvironment, and Therapeutic Response

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2024 Aug 12

PMID 39133347

Authors

Zulipiya Abulihaiti

Weihong Li

Liangyu Yang

Haihang Zhang

Ainong Du

Ni Tang

Yanda Lu

Jiangzheng Zeng

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with limited therapeutic options. Hypoxia is a common feature of the tumor microenvironment that reportedly promotes tumorigenesis. Long non-coding RNAs (lncRNAs) are a class of regulatory molecules with diverse functions in cancer biology. This study aimed to identify hypoxia-induced lncRNAs associated with HCC and evaluate their potential as prognostic and therapeutic biomarkers.

Methods: We employed microarray and The Cancer Genome Atlas (TCGA) data to identify hypoxia-induced lncRNAs in HCC. Subsequently, we focused on CTD-2510F5.4, a candidate lncRNA, and predicted its functional roles in HCC using Gene Ontology (GO) and Guilt-by-Association (GBA) analyses. We validated its expression under hypoxia in Huh7 and HepG2 cells using RT-PCR. Functional assays, including CCK8, wound-healing, and transwell assays, were performed to assess the effects of CTD-2510F5.4 overexpression on HCC cell proliferation, invasion, and metastasis potential. Furthermore, we investigated the association between CTD-2510F5.4 expression and patient prognosis, tumor mutation signature, immune microenvironment characteristics, and therapeutic response to different treatment modalities.

Results: Our data demonstrated a significant upregulation of CTD-2510F5.4 expression in response to hypoxia. Functional enrichment analyses revealed the involvement of CTD-2510F5.4 in cell cycle regulation, E2F targets, G2M checkpoint control, and MYC signaling pathways. Functionally, CTD-2510F5.4 overexpression promoted HCC cell proliferation, invasion, and metastasis. Patients with high CTD-2510F5.4 expression exhibited a worse prognosis, a higher prevalence of TP53 mutations, increased infiltration by immunosuppressive regulatory T cells, elevated expression of immune checkpoint molecules, and higher TIDE scores indicative of immune dysfunction and exclusion. Notably, patients with low CTD-2510F5.4 expression displayed greater sensitivity to immunotherapy and antiangiogenic therapy, while those with high expression responded better to chemotherapy.

Conclusion: Our findings suggest that CTD-2510F5.4 plays a critical role in HCC progression and immune modulation. Its potential as a prognostic biomarker and a predictor of therapeutic response warrants further investigation for personalized treatment strategies in HCC patients.

Citing Articles

Dysregulation of the SREBP pathway is associated with poor prognosis and serves as a potential biomarker for the diagnosis of hepatocellular carcinoma.

Li X, Wang Y, Liu J, Gao T, Cao L, Yan M Mol Med Rep. 2025; 31(5).

PMID: 40017126 PMC: 11894594. DOI: 10.3892/mmr.2025.13477.

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