ObjectivesThe aim of the study was to study the role of dysregulated expression of a microRNA (miRNA), miR-503, in non-small-cell lung cancer (NSCLC) and investigate the underlying mechanism.MethodsQuantitative real-time PCR (qRT-PCR) and in situ hybridization staining (ISH) were used to evaluate the expression level of miR-503 in NSCLC tissues and paired adjacent tissues. CCK-8, colony formation and flow cytometry were performed to explore the effects of miR-503 overexpression on cell proliferation, colony formation and apoptosis. Cells with miR-503 overexpression were used to initiate xenograft models. Dual luciferase reporter assay, qRT-PCR, immunohistochemistry and Western blotting were conducted to investigate the interaction of miR-503 and its potential target.ResultsSignificantly downregulated miR-503 was found in NSCLC tumor tissues and cell lines. miR-503 overexpression significantly inhibited NSCLC cell proliferation, migration and invasion. PDK1 was predicted as the direct targets of miR-503. PDK1 overexpression reversed the inhibitory effects of miR-503 on biological functions, while PDK1 silencing significantly counteracted miR-503 inhibitor-induced pro-tumor effects in A549 cells. Mechanistically, upregulation of miR-503 inhibited PDK1 expression and subsequently caused the inactivation of PI3K/AKT pathway.ConclusionOur results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.

Over the past few decades, it has been demonstrated that hyperglycemia can promote lung carcinoma growth, potentially through significantly increased glucose metabolism; however, the underlying mechanism remains to be fully elucidated. In the present study, treatment with a high concentration of glucose (HG) significantly promoted the proliferation and migration of A549 cells. Receptor for advanced glycation end‑products (RAGE) has previously been demonstrated to be associated with diabetes mellitus and oxidative stress, and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are considered to be initiating factors of oxidative stress. Therefore, an MTT assay, wound‑healing assay, quantitative polymerase chain reaction and western blotting assays were used to analyze the RAGE‑NOX‑4 pathway and to determine its potential involvement in glycometabolism‑associated tumorigenesis. The present study demonstrated that HG could increase the protein expression of RAGE and NOX‑4, whereas the inhibitor of RAGE (anti‑RAGE antibody) could suppress this effect. Futhermore, the inhibitor of NOX [diphenyl iodonium chloride (DPI)] could reduce the protein expression of RAGE and NOX‑4. Furthermore, inhibition of RAGE led to the downregulation of vascular endothelial growth factor (VEGF) and hypoxia‑inducible factor‑1α (HIF‑1α), thus suggesting that HG may influence angiogenesis and tumor metabolism via the RAGE‑NOXs pathway. The present study also demonstrated that the RAGE‑blocking antibody downregulated NOX‑4 and subsequently reduced the production of downstream inflammatory factors, whereas DPI did not affect the mRNA expression of RAGE but it did reduce the protein level of RAGE and then attenuate the inflammatory response. These results indicated that inhibition of RAGE or NOXs may promote the reduced expression of VEGF and HIF‑1α, and NOXs may be downstream targets of RAGE, thus indicating a HG‑RAGE‑NOXs‑VEGF/HIF‑1α association. Furthermore, the results indicated that HG may serve a role in the development of lung adenocarcinoma, mediated by the RAGE‑oxidative stress pathway; therefore, the regulation of this glucose‑associated pathway may be a promising novel direction for oncotherapy. However, while certain antidiabetic agents have been verified to exert inhibitory effects on tumor growth, they can also have long‑term adverse effects on the body, which may limit the value of these drugs as anticancer treatments. In conclusion, the present study suggested a novel attempt to suppress glucose‑induced tumor growth using a RAGE inhibitor such as soluble RAGE while avoiding the risk of glucose fluctuation.

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Potato (Solanum tuberosum L.) cv. Eshu 10 was used to investigate the effects of exogenous gibberellic acid (GA3), abscisic acid (ABA), and low-temperature stress on changes of hormone content, expression patterns of StTCP15 gene, and tuber dormancy characteristics. Under GA3 treatment and low-temperature stress, tuber dormancy was broken in about one week sooner compared with the control group, but ABA treatment did not significantly promote the breaking of tuber dormancy. The results of hormone determination using liquid chromatography-mass spectrometry (LC-MS/ MS) showed that the content of ABA in tubers treated with GA3 or low-temperature stress was lower than in the control group, and it was higher than in the control group under ABA treatment. The GA3 content of tubers was higher than in the control group under GA3 treatment and lower under low-temperature stress. During dormancy, the ABA content continued to increase and GA3 content fluctuated, ABA content rapidly decreased and GA3 content rapidly increased when the dormancy was breaking, and both ABA content and GA3 content increased during germination. The results from the assay of real-time quantitative PCR showed that the expression of the StTCP15 gene was continuously increased during the dormant period in all groups, and the expression of the StTCP15 gene was the highest at the time of dormancy release. The expression of the StTCP15 gene was increased about 15 times on the 7 th d under low-temperature stress and was restored at room temperature. Thus, the StTCP15 gene can respond to GA3, ABA, and low-temperature stress and may be involved in the release of potato tuber dormancy.