Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment
| Autor: | Liming Lu, Chenli Xie, Lingling Zhu, Shizhen Chen, Jiachun Lu, Duo Zhang, Jun Liu, Yuyuan Zeng, Li Liu, Zhuxiang Zhao, Jianfeng Xian, Lei Yang, Boqi Rao, Jinbin Chen, Fuman Qiu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Cancer Research Lung Neoplasms Exosomes TNFAIP3 Metastasis 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung medicine Biomarkers Tumor Humans Protein Isoforms Lung cancer Competing endogenous RNA business.industry Cancer General Medicine medicine.disease Prognosis Microvesicles respiratory tract diseases Gene Expression Regulation Neoplastic Survival Rate 030104 developmental biology 030220 oncology & carcinogenesis Case-Control Studies Cancer research Biomarker (medicine) Tumor necrosis factor alpha Female RNA Long Noncoding business Follow-Up Studies |
| Zdroj: | Carcinogenesis. 42(6) |
| ISSN: | 1460-2180 |
| Popis: | A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-sequencing analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve values as 0.662 [95% confidence interval (CI) = 0.614–0.711] and 0.624 (95% CI = 0.522–0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio = 1.48, 95% CI = 1.05–2.08). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate tumor necrosis factor alpha-induced protein 3 (TNFAIP3) expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE led to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC. |
| Databáze: | OpenAIRE |
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