The aim of this study is to investigate the regulatory mechanism of circPDSS1/miR‐186‐5p/NEK2 axis on the viability and proliferation in gastric cancer (GC) cell line. Differentially expressed circRNAs, miRNAs, and mRNAs in GC tissues and paracarcinoma tissues were analyzed using gene chips GSE83521, GSE89143, and GSE93415. Then, the expression of circPDSS1, miR‐186‐5p, and NEK2 was analyzed via quantitative real‐time polymerase chain reaction (qRT‐PCR). Survival analysis was adopted to explore the association between the circPDSS1 expression and the prognosis of GC. The effect of circPDSS1 on GC cell cycle and apoptosis was verified with the flow cytometry. Targeting relationships among circPDSS1, miR‐186‐5p, and NEK2 were predicted via bioinformatics analysis and demonstrated by the dual‐luciferase reporter assay. Our results showed that circPDSS1 and NEK2 were high‐expressed whereas miR‐186‐5p was low‐expressed in GC tissues and cells. CircPDSS1 promoted GC cell cycle and inhibited apoptosis by sponging miR‐186‐5p, while miR‐186‐5p inhibited cell cycle and promoted apoptosis by targeting NEK2. Thus, circPDSS1 acts as a tumor promoter by regulating miR‐186‐5p and NEK2, which could be a potential biomarker and therapeutic target for the management of GC.
Long non‐coding RNA MIF‐AS1 (lncMIF‐AS1) has been found to be upregulated in the tumor tissues of gastric cancer; however, its importance for the progression of gastric cancer remains unknown. Thus, the present study was designed to determine the role of the lncMIF‐AS1‐based signal transduction pathway in mediating the proliferation and apoptosis of gastric cancer cells. Differentially expressed lncRNAs and mRNAs were screened out using microarray analysis, based on the published data (GSE63288), and validated using quantitative RT‐PCR. Target relationships between lncRNA‐micro RNA (miRNA) and miRNA‐mRNA were predicted by bioinformatics analysis and verified by dual‐luciferase reporter assay. Protein expression of NDUFA4, COX6C and COX5B was detected by western blot. Cell proliferation, cell cycle and apoptosis were determined using colony formation assay and flow cytometry analysis. Oxidative phosphorylation in gastric cancer cells was assessed by levels of oxygen consumption and ATP synthase activity. Expression of lncMIF‐AS1 and NDUFA4 were upregulated in gastric cancer tissues and cells as compared with non‐cancerous gastric tissues and cells (P < .05). MiR‐212‐5p was identified as the most important miRNA linker between lncMIF‐AS1 and NDUFA4, which was negatively regulated by lncMIF‐AS1 and its depletion is the main cause of NDUFA4 overexpression (P < .01). The upregulated expression of NDUFA4 then greatly promoted the proliferation and decreased the apoptosis of gastric cancer cells through activation of the oxidative phosphorylation pathway. Taken together, the present study implies that inhibition of lncMIF‐AS1/miR‐212‐5p/NDUFA4 signal transduction may provide a promising therapeutic target for the treatment of gastric cancer.
Colorectal cancer (CRC) is the third most common tumor worldwide, and recent epidemiological studies have indicated that obesity contributes to the morbidity and mortality of CRC. Furthermore, obesity‐related adipokines have been shown to be closely related to the incidence of CRC, but the underlying mechanisms are unclear. Here, we investigated the effects of high‐fat diet‐induced adipokines and cytokines on the development of CRC in vitro and in vivo. For the in vivo assays, we divided 2‐week‐old C57BL/6J‐ApcMin/J male mice into three groups: normal‐fat diet (ND), high‐fat and high‐sugar feed (HFHS), and high‐fat and low‐sugar feed (HFLS). After 1 week, all mice were injected with 20 mg·kg−1 1,2‐dimethylhydrazine once weekly for 10 consecutive weeks. Body weight, liver weight, epididymal fat weight and blood glucose levels were greatly increased in HFHS and HFLS groups compared with the ND group, and the expression levels of some adipokines and cytokines were obviously higher in HFHS or HFLS mice compared with ND mice. For the in vitro assays, HCT116 CRC cells were treated with sera of ND, HFHS or HFLS groups, or serum‐free media as a negative control. We observed that sera derived from HFHS or HFLS mice that contain excess adipokines and cytokines promoted the proliferation, migration and invasion of HCT116 cells compared with the ND sera‐conditioned medium or serum‐free medium group. Therefore, high‐fat diet‐induced adipokines and cytokines may promote the progression of CRC in vivo and in vitro.
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