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Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5′-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.

Previous studies have demonstrated that microRNAs (miRs) are involved in the carcinogenesis of colorectal cancer (CRC). To the best of our knowledge, the function and regulatory role of miR-532-5p in human CRC remains unknown. The aim of the present study was to determine the role and regulation of miR-532-5p in CRC. Using the reverse transcription-quantitative polymerase chain reaction, it was demonstrated that miR-532-5p was upregulated, whereas runt-related transcription factor 3 (RUNX3) was downregulated in CRC tissues. The upregulated miR-532-5p was associated with the downregulated RUNX3. Furthermore, the two biomarkers were associated with numerous clinicopathological characteristics of CRC, including tumor stage, lymph node involvement, differentiation, vessel invasion and tumor recurrence. The luciferase reporter assay demonstrated that transfection with miR-532-5p mimic markedly downregulated the RUNX3 mRNA and protein levels, via specific binding to the 5'-untranslated region of in human HT-29 CRC cells. In addition, an MTT assay and a colony formation assay demonstrated that miR-532-5p overexpression led to increased tumor cell viability and colony formation ability of HT-29 cells. In conclusion, the results of the present study indicate that miR-532-5p may function as an oncogenic miRNA by promoting cell growth in human CRC cells, and such promotion is associated with the targeted inhibition of RUNX3.

Ion channels are involved in regulating cell proliferation and apoptosis (programed cell death). Since increased cellular proliferation and inhibition of apoptosis are characteristic features of tumorigenesis, targeting ion channels is a promising strategy for treating cancer. CLC-3 is a member of the voltage-gated chloride channel superfamily and is expressed in many cancer cells. In the plasma membrane, CLC-3 functions as a chloride channel and is associated with cell proliferation and apoptosis. CLC-3 is also located in intracellular compartments, contributing to their acidity, which increases sequestration of drugs and leads to chemotherapy drug resistance. In this review, we summarize the recent findings concerning the involvement of CLC-3 in cancer and explore its potential in cancer therapy.

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Disintegrin and metalloproteinase domain-containing proteins (ADAMs) have been implicated in cell adhesion, signaling and migration. The aim of the present study was to identify key members of the ADAM protein family associated with the metastasis of gastric cancer and to evaluate their clinical significance. A total of 193 patients with gastric cancer and positive lymph node metastasis were enrolled. Key members of the ADAM family associated with lymph node metastasis were identified. The correlations between survival times and the clinicopathological features of patients were investigated. Furthermore, ADAM17 expression in gastric cancer cells with different metastatic potentials was determined. ADAM17 was overexpressed in BGC-823 cells and suppressed in SGC-7901 cells to further investigate its effects on cell viability and migration. The key pathways associated with ADAM17 were identified by gene set enrichment analysis (GSEA). It was found that ADAM9 and ADAM17 were significantly upregulated in gastric cancer and positive metastatic lymph node tissues. Further, there was a strong correlation between the survival times of patients and ADAM17 expression. ADAM17 was upregulated in gastric cancer cells with high metastatic potential. The viability of BGC-823 cells significantly increased following ADAM17 overexpression, whereas the viability and migration of SGC-7901 cells decreased following ADAM17 suppression. GSEA and western blot analysis revealed a positive correlation between the Notch and Wnt signaling pathways with ADAM17 expression. In conclusion, the increased expression of ADAM17 promoted the progression of gastric cancer, potentially via Notch and/or Wnt signaling pathway activation, and ADAM17 may serve as a useful prognostic marker.

The flight deck of commercial aircraft is sophisticated and searching for the necessary information at the right time is sometimes challenging. This research investigates pilot's visual parameters while interacted with two different designs of crew alerting system by eye tracking technology. There are 24 aviation professionals that participated in this experiment including commercial pilots, private pilots and avionic engineers. Compared with traditional design, the new integrated design applied proximity compatibility principles to assist pilots in searching necessary information to deal with urgent situations. The results demonstrated that the integrated design is superior to traditional design in providing accurate instructions as determined by visual behaviors. However, the integrated design increases pilot's situation awareness by redirecting attention from current task to the most critical task with the cost of a longer total fixation duration time. Pilot's visual parameters demonstrated significant differences while interacting with PFD mainly numeric, ND mostly by symbols and EICAS with presented text messages. Therefore, flight deck design has to adopt a holistic approach as pilot's visual attentions is shifting among all types of different displays to gain situation awareness rather than focus on only one display. The design of integrated EICAS can provide detailed instructions to deal with urgent situations which induced higher cognitive loads as pilot's pupil dilation is significant bigger than interacted with traditional design. By eye tracking technology, it is applicable to design human-centered flight decks to improve safety and human performance in aviation.