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Background: Gastric cancer (GC) is a malignant tumor of digestive tract with high mortality. Elucidating the molecular mechanisms of GC and obtaining new molecular targets are particularly important for the prevention and treatment of GC. The discovery of long non-coding RNAs (lncRNAs) provides the possibility for further elucidating the molecular mechanisms of GC and discovering new molecular markers. Aim: Here, we aimed to explore the function and the mechanism of lncRNA PITPNA-AS1 in GC. Methods: High-throughput lncRNA microarray was used to compare the differences in expression profiles between tumor tissues and adjacent tissues, and to filtrate the differentially expressed lncRNAs in tumors. To analyze the relationship between lncRNA expression and clinicopathological parameters in GC. The apoptosis was detected by down-regulation of lncRNA. The effect of down-regulated lncRNA PITPNA-AS1 on the migration and invasion of GC cells was determined by wound healing and Transwell assays. The function of lncRNA PITPNA-AS1 on tumor growth was verified by tumor experiment in nude mice. Analysis of target interaction relationship was performed by luciferase assay. Results: The results of high throughput chip analysis identified that PITPNA-AS1 was up-regulated in GC tissues. Our data revealed that knockdown of PITPNA-AS1 was able to inhibit tumor development of GC cells. Meanwhile, PITPNA-AS1 could regulate SOX4 expression via targeting miR-92a-3p. Conclusion: Thus, we concluded that PITPNA-AS1 induced the development of GC cells by inhibiting miR-92a-3p and inducing SOX4. Our finding presents novel insights of GC, which may provide an underlying therapeutic target for GC treatment.

This study aims to examine whether miR-448 reverses the cisplatin (DDP) resistance in lung cancer by modulating SATB1. QRT-PCR and immunohistochemistry were used to examine the miR-448 and SATB1 expressions in DDP-sensitive and -resistant lung cancer patients. A microarray was used to investigate the cytoplasmic/nucleic ratio (C/N ratios) of genes in A549 cells targeted by miR-448, followed by Dual-luciferase reporter gene assay. A549/DDP cells were transfected with miR-448 mimics/inhibitors with or without SATB1 siRNA followed by MTT assay, Edu staining, flow cytometry, qRT-PCR and western blotting. MiR-448 was lower but SATB1 was increased in DDP-resistant patients and A549/DDP cells. And the patients showed low miR-448 expression or SATB1 positive expression had poor prognosis. SATB1, as a target gene with higher C/N ratios (>1), was found negatively regulated by miR-448. Besides, miR-448 inhibitors increased resistance index of A549/DDP cells, promoted cell proliferation, increased cell distribution in S phrase, declined cell apoptosis and activated Wnt/β-catenin pathway. However, SATB1 siRNA could reverse the above effect caused by miR-448 inhibitors. MiR-448 targeting SATB1 to counteract the DDP resistance of lung cancer cells via Wnt/β-catenin pathway.

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