Discovery of a Novel Linc01125 Isoform in Serum Exosomes Predicts Onset and Poor Prognosis of NSCLC

2021 
Background: A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. Methods: We employed RNA-Seq analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined diagnostic and prognostic value of a promising lncRNA in four datasets. Findings: We identified several dysregulated lncRNAs and found that those up-regulated lncRNAs in NSCLC were mostly tumor-suppressive, while down-regulated lncRNAs were most oncogenic. The most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, and its expression was also correlated with prognosis. Clinic treatment decreased serum exosomal linc01125 in NSCLC patients. Linc01125 functions to inhibit cancer growth and metastasis. Acting as a competing endogenous RNA, linc01125 sponges several microRNAs (miRs) to regulate gene expression such as TNFAIP3 via binding miR-19b-3p. Notably, oncogenic transformation of 16HBE leads to decreased linc01125 in cells but increased linc01125 in cells-derived exosomes. Linc01125 expression in exosomes was also highly correlated with that in tumor-associated exosomes. Linc01125 could be loaded into exosomes in vitro and in vivo, which did not dampen tumor development. Interpretation: Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting prognosis of NSCLC. Funding: National Natural Scientific Foundation of China, Guangzhou Science and Technology Program Pearl River Nova projects, The National Key Research and Development Program of China, Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the institutional review board of Guangzhou Medical University.
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