GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Jin, Yixiang; Jin, Wenxu; Zheng, Zhouci; Chen, Endong; Wang, Qingxuan; Wang, Yinghao; Wang, Ouchen; Zhang, Xiaohua
Abstract
Background: Thyroid cancer is a common malignant tumor of the endocrine system. Its incidence has increased continuously worldwide for the past three decades. With advanced sequencing technology, we discovered that GABRB2 gene is overexpressed in tumor tissues and closely associated with vertebrate nervous systems. However, its role in cancer remains unclear. Methods: We conducted a massively parallel whole transcriptome resequencing and a comprehensive analysis of matched papillary thyroid carcinoma (PTC) tumors and normal tissues in 19 patients. Results showed that GABRB2 expression was significantly upregulated in thyroid cancer. Forty-five pairs of tumors and normal tissues were subjected to reverse transcription polymerase chain reaction to validate previous findings. The specific functions of GABRB2 in PTC cell lines (BCPAP, TPC1, and KTC-1) transfected with small interfering RNA were determined through cell colony formation, Cell Counting Kit-8, Transwell migration, Transwell invasion, and apoptosis assays. The effect of DNA demethylation on this gene was also examined. Results: GABRB2 was remarkably overexpressed in primarily sequenced FTC tumors and validation cohort (T: N = 4.94 +/- 3.43:0.83 +/- 1.71, P < 0.001), and this observation was consistent with that in the TCGA cohort (T: N = 38.92 +/- 35.53:0.30 +/- 0.55, P < 0.001). GABRB2 overexpression was correlated with lymph node metastasis in both cohorts (P < 0.01). In vitro experiments revealed that GABRB2 down regulation significantly inhibited the colony formation, migration, and invasion of the three PTC cell lines. Conclusion: GABRB2 plays important tumorigenic functions and acts as a novel oncogene in PTC. 2017 Published by Elsevier Inc.
Subregional Expression of Hippocampal Glutamatergic and GABAergic Genes in F344 Rats with Social Isolation after Weaning
COMPARATIVE MEDICINE
Authors: Iwata, Hisaya; Yamamuro, Yutaka
Abstract
Many studies have shown that postweaning social isolation (pwSI) alters various behavioral phenotypes, including hippocampus-dependent tasks. Here, we report the comprehensive analysis of the expression of glutamatergic and GABAergic neurotransmission related genes in the distinct hippocampal subregions of pwSI rats. Male F344 rats (age, 4 wk) experienced either pwSI or group housing (controls). At 7 wk of age, the hippocampus of each rat was removed and laser-microdissected into the CA1 and CA3 layers of pyramidal cells and the granule cell layer of the dentate gyrus. Subsequently, the expression of glutamatergic- and GABAergic-related genes was analyzed by quantitative RT-PCR. In the CA1 and CA3 pyramidal cell layers, 18 of 24 glutamate receptor subunit genes were at least 1.5-fold increased in expression after pwSI. In particular, the expression of several N-methyl-D-aspartate and kainate receptors (for example, Grin2a in CA1, Grik4 in CA3) was significantly increased after pwSI. In contrast, pwSI tended to decrease the expression of GABA(A) receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the group-housed rats. These results indicate a subregion specific increase of glutamate receptors and reduction of GABA(A) receptors, suggesting that the hippocampal circuits of pwSI rats may be in more excitable states than those of group-housed rats.