Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665–miR98–AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

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Diagnosis and treatment at an early stage may improve survival of non-small-cell lung cancer (NSCLC). Previous studies have found that long noncoding RNA growth arrestspecific transcript 5 (GAS5) is essential to cancer progression. However, the expression and diagnostic value of GAS5 in exosomes (Exo-GAS5) remain unclear. One hundred and four participants were enrolled, including subjects with NSCLC (n = 64) and healthy subjects (n = 40). The total Exosome Isolation Kit was applied to isolate exosomes from serum. Total RNA was extracted and the AS5 expression was analyzed using quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic value of Exo-GAS5 in NSCLC. Our data indicated that the Exo-GAS5 was downregulated in patients with NSCLC compared with healthy controls (p < 0.001). Furthermore, patients with NSCLC with larger tumor size (p = 0.025) and advanced TNM (T: extent of the primary tumor; N: lymph node involvement; M: metastatic disease) classification (p = 0.047) showed lower Exo-GAS5 expression. ROC curve analysis using Exo-GAS5 combined with carcinoembryonic antigen showed an area under curve (AUC) of 0.929. Exo-GAS5 could be used to distinguish patients with Stage I NSCLC with an AUC of 0.822. In conclusion, Exo-GAS5 may function as an ideal noninvasive serum-based marker for identifying patients with early NSCLC. K E Y W O R D Sbiomarker, exosomes, GAS5, NSCLC

Purpose: Lung adenocarcinoma (LUAD) is a main subtype of lung cancer, which is the leading cause of cancer-related deaths. The five-year survival rates of lung cancer patients are still comparatively low. Therefore, potential therapeutic targets are urgently needed to improve the survival of lung cancer patients. In this study, we identified FAM111B as an oncogene and potential therapeutic target for LUAD. Methods: The TCGA database and tissue microarray analysis were used to compare the expression of FAM111B in tumor tissue and normal tissues and evaluate the relationship between FAM111B expression and clinical survival. FAM111B was knocked down and overexpressed to observe whether FAM111B could affect the proliferation, migration, cell cycle, and apoptosis of LUAD cells in vivo and in vitro. Results: FAM111B was highly expressed in tumor tissues compared with normal tissues ( P <0.01). LUAD patients with hyper-expression of FAM111B had a lower recurrence-free survival ( P <0.01) and shorter overall survival ( P <0.01). Knocking down FAM111B inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Silencing FAM111B could arrest LUAD cells at G2/M phase and increase apoptosis. Overexpression of FAM111B promoted the growth of lung cancer cells. FAM111B was identified as a direct target of p53 in existing researches by chip-seq analysis. Bioinformatics analysis predicted that FAM111B could directly bind to BAG3 (BCL2 associated athanogene 3). When FAM111B was down-regulated, both expression of BAG 3 and BCL2 were significantly reduced, whereas decreasing the expression of BAG3 had no effect on FAM111B. Conclusions: Our study indicated that FAM111B might be an oncogene and potential therapeutic target in LUAD which could be involved in the regulation of tumor cells by p53 signaling pathway and play an important role in the process of cell cycle and apoptosis by influencing the expression of BAG3 and BCL2.