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GABRB2在甲状腺乳头状癌的淋巴结转移中起重要作用。

GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer.

作者信息

Jin Yixiang, Jin Wenxu, Zheng Zhouci, Chen Endong, Wang Qingxuan, Wang Yinghao, Wang Ouchen, Zhang Xiaohua

机构信息

Departments of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Departments of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Biochem Biophys Res Commun. 2017 Oct 21;492(3):323-330. doi: 10.1016/j.bbrc.2017.08.114. Epub 2017 Aug 30.

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 PTC 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 downregulation 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.

摘要

背景

甲状腺癌是内分泌系统常见的恶性肿瘤。在过去三十年中,其发病率在全球范围内持续上升。随着先进测序技术的出现,我们发现GABRB2基因在肿瘤组织中过表达,且与脊椎动物神经系统密切相关。然而,其在癌症中的作用仍不清楚。

方法

我们对19例患者的配对甲状腺乳头状癌(PTC)肿瘤组织和正常组织进行了大规模平行全转录组重测序及综合分析。结果显示,GABRB2在甲状腺癌中表达显著上调。对45对肿瘤组织和正常组织进行逆转录聚合酶链反应以验证先前的发现。通过细胞集落形成、细胞计数试剂盒-8、Transwell迁移、Transwell侵袭和凋亡检测,确定了用小干扰RNA转染的PTC细胞系(BCPAP、TPC1和KTC-1)中GABRB2的具体功能。还检测了DNA去甲基化对该基因的影响。

结果

GABRB2在初次测序的PTC肿瘤组织和验证队列中显著过表达(肿瘤组织:正常组织=4.94±3.43:0.83±1.71,P<0.001),这一观察结果与TCGA队列中的情况一致(肿瘤组织:正常组织=38.92±35.53:0.30±0.55,P<0.001)。在两个队列中,GABRB2过表达均与淋巴结转移相关(P<0.01)。体外实验表明,GABRB2下调显著抑制了三种PTC细胞系的集落形成、迁移和侵袭。

结论

GABRB2发挥重要的致瘤功能,是PTC中的一种新型癌基因。

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