Oncogenic Effect of the Novel Fusion Gene VAPA-Rab31 in Lung Adenocarcinoma.

Fusion genes have been identified as oncogenes in several solid tumors including lung, colorectal, and stomach cancers. Here, we characterized the fusion gene, VAPA-Rab31, discovered from RNA-sequencing data of a patient with lung adenocarcinoma who did not harbor activating mutations in EGFR, KRAS and ALK. This fusion gene encodes a protein comprising the N-terminal region of vesicle-associated membrane protein (VAMP)-associated protein A (VAPA) fused to the C-terminal region of Ras-related protein 31 (Rab31). Exogenous expression of VAPA-Rab31 in immortalized normal bronchial epithelial cells demonstrated the potential transforming effects of this fusion gene, including increased colony formation and cell proliferation in vitro. Also, enhanced tumorigenicity upon VAPA-Rab31 was confirmed in vivo using a mouse xenograft model. Metastatic tumors were also detected in the liver and lungs of xenografted mice. Overexpression of VAPA-Rab31 upregulated anti-apoptotic protein Bcl-2 and phosphorylated CREB both in cells and xenograft tumors. Reduced apoptosis and increased phosphorylation of CREB and Erk were observed in VAPA-Rab31-overexpressing cells after bortezomib treatment. Elevated Bcl-2 level via activated CREB contributed to the resistance to the bortezomib-induced apoptosis. Our data suggest the oncogenic function of the novel fusion gene VAPA-Rab31 via upregulated Bcl-2 and activated CREB in lung cancer.

Complementary Metal-Oxide-Semiconductor Symmetric Current-Conveyor Transimpedance Amplifier.

This paper presents a novel symmetric current-conveyor transimpedance amplifier (SCC-TIA) implemented in a 0.13-µm CMOS technology for the applications of LiDAR systems, where a modifiedcascode configuration is newly proposed for input current buffer to deliver the photo-currents to the following voltage-mode inverter TIA without signal loss. Measured results of the proposed SCC-TIA demonstrate 69-dBΩ transimpedance gain, 410-MHz bandwidth, 13-pA/sqrt (Hz) average noise current spectral density, and 20-mW power dissipation from a single 1.2-V supply. Chip core occupies the area of 280×130 µm².

Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells.

Galanin is a 30 amino-acid active neuropeptide that acts via three G-protein coupled galanin receptors, GALR1, GALR2 and GALR3. Recently, GALR1 was also suggested as a tumor suppressor gene that was frequently silenced in head and neck squamous cell carcinoma; moreover, galanin and GALR1 were reported to inhibit human oral cancer cell proliferation. However, the exact role of galanin in gastric cancer is unclear. Here, we describe the epigenetic silencing of galanin in human gastric cancer. Five gastric cancer cell lines (SNU-1, SNU-601, SNU-638, KATOIII, and AGS) showed a significant reduction in galanin expression that was restored by the demethylating agent 5-aza-2'-deoxycytidine. We confirmed the hypermethylation of CpG islands in the galanin promoter region by methylation-specific and bisulfate sequencing polymerase chain reaction (PCR). Interestingly, hypermethylated galanin did not affect galanin receptor expression. Exogenous galanin expression in silenced cells induced apoptosis and decreased phosphorylated Akt expression. Taken together, these data suggest that galanin hypermethylation impairs its tumor suppressor function in gastric cancer carcinogenesis.