Hypoxia-induced LncRNA CTD-2510F5.4 facilitates hepatocellular carcinoma cell proliferation and invasion, predicts prognosis, tumor microenvironment, and drug efficacy in patients with hepatocellular carcinoma

Abstract

Abstract Purpose Hypoxia induces abnormal expression of various long non-coding RNAs (LncRNAs) highly correlated with tumorigenesis. In this study, we identified CTD-2510F5.4, a hypoxia-induced LncRNA, based on microarray and TCGA analyses, and evaluated its impact on HCC prognosis, tumor microenvironment (TME), and drug efficacy. Methods We cultured Huh7 cells in a hypoxic chamber and detected CTD-2510F5.4 expression levels using RT-PCR analysis. Then we tested the effects of CTD-2510F5.4 overexpression on cell proliferation, invasion, and metastasis potential using CCK8, wound-healing, and transwell assays, respectively. We performed GO and Guilt-by-Association (GBA) correlation analysis to predict CTD-2510F5.4 functions. Besides, mutation signature, immune characteristics, and therapeutic response prediction between high- and low-CTD-2510F5.4 groups were further compared. Results Our results showed that CTD-2510F5.4 expression markedly increased under hypoxia and significantly promoted HCC cell proliferation, invasion, and metastasis. Functional enrichment analyses revealed that CTD-2510F5.4 is involved in cell proliferation and various tumor-related signaling pathways, including cell cycle, E2F targets, G2M checkpoint, and MYC targets V1. Patients with high CTD-2510F5.4 expression rates are preferentially associated with worse prognosis, higher TP53 mutation rates, higher infiltration by immune-suppressive regulatory cells, expressed immune checkpoints at elevated levels, and higher TIDE scores. The half-maximal inhibitory concentration (IC50) indicated that patients with low CTD-2510F5.4 expression are more responsive to immunotherapy and antiangiogenic targeted therapy, whereas those with high CTD-2510F5.4 expression are more sensitive to chemotherapy. Conclusion Our findings suggest that CTD-2510F5.4 could be a valuable biomarker for guiding the personalized treatment of HCC patients.