BackgroundAccumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown.MethodsHOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis.ResultsHOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers.ConclusionsHOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.

Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27 kip1 expression by targeting one binding site in the 3 0 -untranslated region (3 0 -UTR) of p27 kip1 mRNA. qPCR and Western blot assays verified that miR-196a reduced p27 kip1 expression at both mRNA and protein levels. The p27 kip1 -mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27 kip1 expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27 kip1 could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.

Simultaneous detection of both ion flux and membrane potential in vivo and in situ in plants is a challenging research task. To explore the mechanisms of plant electrical activity, researchers urgently need to understand and determine the types of ions and the ion fluxes that pass in and out of cells during polarization and repolarization, but the required measurements are very difficult to perform. In this paper, we have developed a versatile system that can detect the ionic flux and the membrane potential, in vivo and in situ, simultaneously. The system uses a self-referencing ion-selective glass microelectrode and a membrane potential glass microelectrode as sensors. These sensors are linked through a preamplifier with high input impedance to a specific dynamic measurement system that can amplify small extracellular concentration gradient signals and realize simultaneous measurement of both the ion flux and the membrane potential. In addition, an interpolation fitting algorithm has been proposed to reduce the artifacts that are present in the in situ measurements during plant growth. The hydrogen ion fluxes in wheat roots were measured using the self-referencing ion-selective microelectrodes, and the proposed system was used to measure NaCl stimulation-induced changes in the membrane potentials and hydrogen ion fluxes of wheat root epidermal cells. The results demonstrate that the system can meet the ion flux and membrane potential measurement requirements. INDEX TERMS Ion flux, membrane potential, microelectrode sensor, multi-channel recording system, plant electrical signal, weak signal detection.