Identification of a novel lncRNA prognostic signature and analysis of functional lncRNA AC115619.1 in hepatocellular carcinoma

Binliang Gan; Youwu He; Yonggang Ma; Linfeng Mao; Chuanjie Liao; Ganlu Deng

doi:10.3389/fphar.2023.1167418

Identification of a novel lncRNA prognostic signature and analysis of functional lncRNA AC115619.1 in hepatocellular carcinoma

Front Pharmacol. 2023 Aug 8:14:1167418. doi: 10.3389/fphar.2023.1167418. eCollection 2023.

Authors

Binliang Gan^{1

2}, Youwu He^{1

3}, Yonggang Ma⁴, Linfeng Mao^{3

5}, Chuanjie Liao^{1

3}, Ganlu Deng^{1

3}

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
² Department of Oncology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
³ Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China.
⁴ Department of NeuroInterventional Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, China.
⁵ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Abstract

Background: Hepatocellular carcinoma (HCC) is the deadliest malignancy. Long non-coding RNAs (lncRNAs) are involved in the development of multiple human malignancies. This study aimed to establish a reliable signature and identify novel biomarkers for HCC patients. Methods: Differentially expressed lncRNAs (DElncRNAs) were identified from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate, LASSO, and multivariate Cox regression analyses were applied to screen the prognostic lncRNAs and establish a prognostic model. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses were conducted to validate the prognostic value of this model. The association between lncRNAs and differential m6A genes was analyzed by Spearman's analysis. A series of bioinformatic and in vitro experiments were applied to explore the function of hub lncRNA. Results: A total of 32 DElncRNAs were identified, and 12 DElncRNAs were associated with the prognosis of HCC patients. A prognostic signature comprising six prognostic lncRNAs (LINC02428, LINC02163, AC008549.1, AC115619.1, CASC9, and LINC02362) was constructed, and the model exhibited an excellent capacity for prognosis prediction. Furthermore, 12 differential m6A regulators were identified, and RBMX was found to be correlated negatively with the hub lncRNA AC115619.1. The expression level of AC115619.1 was lower in HCC tissues than that in normal tissues and was significantly related to clinicopathologic features, survival rate, and drug sensitivity. Overexpression of AC115619.1 notably inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: This study provided a promising prognostic signature for HCC patients and identified AC115619.1 as a novel biomarker, which plays an essential role in regulating the progression of HCC.

Keywords: biomarker; diagnosis; hepatocellular carcinoma; long non-coding RNA; prognosis.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81902500), the China Postdoctoral Science Foundation (2022MD723764), and the Guangxi Natural Science Foundation (No. 2023GXNSFBA026108).