Identification of prognosis-related lncRNAs and cell validation in lung squamous cell carcinoma based on TCGA data

Yishuang Cui; Yanan Wu; Mengshi Zhang; Yingze Zhu; Xin Su; Wenyue Kong; Xuan Zheng; Guogui Sun

doi:10.3389/fonc.2023.1240868

Identification of prognosis-related lncRNAs and cell validation in lung squamous cell carcinoma based on TCGA data

Front Oncol. 2023 Oct 25:13:1240868. doi: 10.3389/fonc.2023.1240868. eCollection 2023.

Authors

Yishuang Cui¹, Yanan Wu¹, Mengshi Zhang¹, Yingze Zhu¹, Xin Su¹, Wenyue Kong¹, Xuan Zheng¹, Guogui Sun²

Affiliations

¹ School of Public Health, North China University of Science and Technology, Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.
² Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.

Abstract

Objective: To discern long non-coding RNAs (lncRNAs) with prognostic relevance in the context of lung squamous cell carcinoma (LUSC), we intend to predict target genes by leveraging The Cancer Genome Atlas (TCGA) repository. Subsequently, we aim to investigate the proliferative potential of critical lncRNAs within the LUSC milieu.

Methods: DESeq2 was employed to identify differentially expressed genes within the TCGA database. Following this, we utilized both univariate and multivariate Cox regression analyses to identify lncRNAs with prognostic relevance. Noteworthy lncRNAs were selected for validation in cell lines. The intracellular localization of these lncRNAs was ascertained through nucleocytoplasmic isolation experiments. Additionally, the impact of these lncRNAs on cellular proliferation, invasion, and migration capabilities was investigated using an Antisense oligonucleotides (ASO) knockdown system.

Results: Multivariate Cox regression identified a total of 12 candidate genes, consisting of seven downregulated lncRNAs (BRE-AS1, CCL15-CCL14, DNMBP-AS1, LINC00482, LOC100129034, MIR22HG, PRR26) and five upregulated lncRNAs (FAM83A-AS1, LINC00628, LINC00923, LINC01341, LOC100130691). The target genes associated with these lncRNAs exhibit significant enrichment within diverse biological pathways, including metabolic processes, cancer pathways, MAPK signaling, PI3K-Akt signaling, protein binding, cellular components, cellular transformation, and other functional categories. Furthermore, nucleocytoplasmic fractionation experiments demonstrated that LINC00923 and LINC01341 are predominantly localized within the cellular nucleus. Subsequent investigations utilizing CCK-8 assays and colony formation assays revealed that the knockdown of LINC00923 and LINC01341 effectively suppressed the proliferation of H226 and H1703 cells. Additionally, transwell assays showed that knockdown of LINC00923 and LINC01341 significantly attenuated the invasive and migratory capacities of H226 and H1703 cells.

Conclusion: This study has identified 12 candidate lncRNA associated with prognostic implications, among which LINC00923 and LINC01341 exhibit potential as markers for the prediction of LUSC outcomes.

Keywords: LINC00923; LINC01341; LUSC; TCGA; lncRNA.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (grant no. H82172658); Supported by the Basic Innovation Team Grant of Precision Diagnosis & Treatment of Small Cell Lung Cancer of Tangshan Medical & Engineering Integration Foundation (grant no. 21130203D); Supported by the Project of High Level Group for Research and Innovation of School of Public Health, North China University of Science and Technology (grant no. KYTD202309). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.