AUTHOR=Fan Yongfei , Zhou Yong , Li Xinwei , Lou Ming , Gao Zhaojia , Yuan Kai , Tong Jichun 

TITLE=Long Non-Coding RNA AL513318.2 as ceRNA Binding to hsa-miR-26a-5p Upregulates SLC6A8 Expression and Predicts Poor Prognosis in Non-Small Lung Cancer

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.781903

DOI=10.3389/fonc.2022.781903

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Studies have demonstrated that the regulatory role of competitive endogenous RNA (ceRNA) networks is closely related to tumorigenesis, which provides new targets for tumor therapy. In this study, the focus was to explore the ceRNA networks that regulate <italic>SLC6A8</italic> expression and their prognosis in non-small cell lung cancer (NSCLC).</p></sec><sec><title>Methods</title><p>Firstly, the Cancer Genome Atlas (TCGA) data combined with immunohistochemical staining was used to compare <italic>SLC6A8</italic> expression in NSCLC tissues and normal tissues. Thereafter, samples from the immunohistochemical staining of NSCLC were integrated with clinical follow-up data for prognostic analysis. The Starbase database was employed to search for <italic>SLC6A8</italic>-targeted miRNAs and lncRNAs, and survival analysis was performed using clinical data from TCGA to obtain <italic>SLC6A8</italic> expression and prognosis-related ceRNA networks. Finally, the prognostic and therapeutic prospects of <italic>SLC6A8</italic> in NSCLC were further analyzed from methylation sites and the immune microenvironment.</p></sec><sec><title>Results</title><p>The study results revealed that <italic>SLC6A8</italic> was significantly overexpressed in NSCLC tissues compared to normal tissues, and clinical follow-up data showed that the overexpression group was associated with poor prognosis. In addition, the Starbase data combined with TCGA clinical data analysis demonstrated that the AL513318.2/hsa-miR-26a-5p/<italic>SLC6A8</italic> network regulates <italic>SLC6A8</italic> overexpression in NSCLC and is associated with poor prognosis. Methylation analysis revealed that 11 methylation sites were closely associated with the prognosis of NSCLC. In addition, the immune prognostic risk model showed that the high-risk group was associated with a poorer prognosis than the low-risk group, despite showing a better immunotherapy outcome.</p></sec><sec><title>Conclusion</title><p>In summary, the AL513318.2/hsa-miR-26a-5p/<italic>SLC6A8</italic> network upregulates <italic>SLC6A8</italic> expression in NSCLC and is associated with poor prognosis. Therefore it may be a prognostic biomarker of NSCLC and a potential therapeutic target.</p></sec>