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

Frontiers in Oncology

Oncology

Guogui Sun¹  Yingze Zhu²  Xin Su²  Wenyue Kong²  Mengshi Zhang²  Yishuang Cui²  Xuan Zheng²  Yanan Wu² 

[1] Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China;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;

关键词: LUSC;    lncRNA;    LINC00923;    LINC01341;    TCGA;   

DOI  :  10.3389/fonc.2023.1240868

 received in 2023-06-15, accepted in 2023-10-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveTo 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.MethodsDESeq2 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.ResultsMultivariate 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.ConclusionThis 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.

【 授权许可】

Unknown   
Copyright © 2023 Cui, Wu, Zhang, Zhu, Su, Kong, Zheng and Sun