circIARS: a potential plasma biomarker for diagnosing non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers in the world, and early diagnosis can effectively improve patient survival. Here, differentially expressed circIARS genes are screened from the sequencing results, and their molecular characteristics are examined by Sanger sequencing, RNase R assay, agarose gel electrophoresis (AGE), and fluorescence in situ hybridization (FISH). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) is performed to detect the expression level of circIARS. The diagnostic value of the signature is analyzed using a subject operating characteristic (ROC) curve. Moreover, plasma is collected from postsurgical, chemotherapy, and relapse patients to investigate the prognostic value of circIARS in NSCLC. The expression of circIARS is greater in both the plasma and tissues of NSCLC patients than in those of healthy individuals, and could be used to distinguish NSCLC patients from patients with benign pulmonary disease (BPD), small cell lung cancer (SCLC) patients, and healthy individuals. The expression level of circIARS relatively decreases after antitumor therapy, such as chemotherapy, and relatively increases after recurrence. ROC analysis reveals that circIARS has better detection efficiency than traditional markers. In addition, circIARS expression level is strongly correlated with several clinicopathological parameters. Finally, we tentatively predict the downstream miRNAs or RBP that might bind to circIARS. Plasma circIARS is significantly greater in NSCLC patients and has good stability and specificity as a diagnostic marker, which could aid in the adjuvant diagnosis and dynamic monitoring of NSCLC.

circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway.

This study aims to explore the role and mechanism of circ-IARS in non-small-cell lung cancer (NSCLC) progression. Expression of circ-IARS, microRNA (miR)-1252-5p, and hepatoma-derived growth factor (HDGF) was measured by real-time quantitative PCR and western blotting. The interactions among circ-IARS, miR-1252-5p, and HDGF were determined by dual-luciferase reporter assay and RNA immunoprecipitation. Cell behaviors were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, scratch wound assay, and transwell assay, and validated in in vivo xenograft model. Exosomes were isolated using commercial kit, and the expression and functions of exosomal circ-IARS (exo-circ-IARS) were analyzed as described above. Results showed that the expression of circ-IARS was upregulated in NSCLC cells, NSCLC tissues, and serum exosomes from NSCLC patients. circ-IARS exhaustion antagonized cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in NSCLC. Molecularly, circ-IARS could sponge miR-1252-5p to modulate the expression of the downstream gene HDGF. In addition, miR-1252-5p downregulation attenuated circ-IARS exhaustion-mediated effects in H1299 and A549 cells. MiR-1252-5p mimic-induced effects were relieved by increasing HDGF expression in H1299 and A549 cells. Exo-circ-IARS promoted H460 cell proliferation, migration, and invasion and inhibited cell apoptosis. Silencing circ-IARS retarded tumor growth of NSCLC cells in vivo. Thus, circ-IARS, secreted by exosomes, was a novel oncogene in NSCLC and regulated the malignant development of NSCLC cells via circ-IARS/miR-1252-5p/HDGF competing endogenous RNA regulatory axis.

Exosomes derived from Nr-CWS pretreated MSCs facilitate diabetic wound healing by promoting angiogenesis via the circIARS1/miR-4782-5p/VEGFA axis.

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.