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BackgroundLinc00152 has been identified highly associated with the tumorigenesis and development of gastric cancer, however, the detailed mechanism of Linc00152 involved still remains unclear.MethodsRT-PCR and western blot were used to detect the expression of Linc00152 and EGFR. The CCK8 and EDU assay was employed to measure cell proliferation while xenotransplantation technology was applied in BALB/C nude mice. The interaction between lncRNA and target protein was investigated by RNA pull-down and RNA immunoprecipitation assay.ResultsIn this study, we first confirmed the upregulation of cytoplasmic expressed Linc00152 in 72 pair tissues of gastric patients. A suppression of cell proliferation and tumor growth was obtained in MGC803 and HGC-27 cells treated with Linc00152 shRNA. RNA pull-down and RIP assay revealed that Linc00152 could directly bind with EGFR which caused an activation of PI3K/AKT signaling.ConclusionWe first found that Linc00152 could promote tumor growth through EGFR-mediated PI3K/AKT pathway which may serve as potential targets for therapy in the future.

Centrosomal protein 55 (CEP55) is the latest found member in the centrosomal relative protein family, which participates in cell-cycle regulation. CEP55 exists in many kinds of normal tissues and tumour cells such as hepatocellular carcinoma, and is important in carcinogenesis. However, the role of CEP55 in the pathogenesis of gastric cancer (GC) remains unclear. The mRNA levels of CEP55 in GC tissues and GC cell lines were examined by quantitative real-time PCR, and the protein expression of CEP55 in GC tissues was detected by Western blot and immunohistochemistry. The role of CEP55 in regulating the proliferation of GC cell lines was investigated both in vitro and in vivo. CEP55 was strongly upregulated in human GC, indicating that CEP55 contributed to carcinogenesis and progression of GC. Ectopic overexpression of CEP55 enhanced the cell proliferation, colony formation, and tumourigenicity of GC cells, whereas CEP55 knockdown inhibited these effects. We discovered that cell transformation induced by CEP55 was mediated by the AKT signalling pathway. Overexpression of CEP55 enhanced the phosphorylation of AKT and inhibited the activity of p21 WAF1/Cip1. In addition, cellular proliferation was suppressed as a result of cell cycle arrest at the G2/M phase in CEP55-knockdown cells. CEP55 expression was elevated in GC compared with normal control tissues. Credible evidence showed that CEP55 can be a potential therapeutic target in GC.

Cisplatin (CDDP) resistance is a major clinical problem associated with poor prognosis in gastric cancer (GC) patients. In this study, we performed integrated analysis of TCGA data from microRNAs (miRNAs) expression matrix of GC patients who received CDDP-based chemotherapy with GEO dataset which contains differential miRNAs expression profiles in CDDP-resistant and -sensitive cell lines. We identified miR-148a-3p downregulation as a key step involved in CDDP resistance. Using a cohort consisting 105 GC patients who received CDDP-based therapy, we found that miR-148a-3p downregulation was associated with a decrease in patients’ disease-free survival (DFS, P=0.0077). A series of experiment data demonstrated that: 1) miR-148a-3p was downregulated in CDDP-resistant GC cell lines; 2) miR-148a-3p reconstitution sensitized CDDP-resistant cells to CDDP treatment through promoting mitochondrial fission and decreasing AKAP1 expression level; 3) AKAP1 played a novel role in CDDP resistance by inhibiting P53-mediated DRP1 dephosphorylation; 4) miR-148a-3p reconstitution in CDDP-resistant cells inhibits the cyto-protective autophagy by suppressing RAB12 expression and mTOR1 activation. Taken together, our study demonstrates that miR-148a-3p could be a promising prognostic marker or therapeutic candidate for overcoming CDDP resistance in GC.

These results provide a mechanism by which AQP3 is upregulated, as well as highlight the importance of miR-874 in gastric cancer development and progression.