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下调整合素亚基 α7(ITGA7)通过调节上皮间质转化促进甲状腺乳头状癌细胞的增殖、侵袭和迁移。

Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition.

机构信息

Department of Thyroid & Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2020 Feb 3;52(2):116-124. doi: 10.1093/abbs/gmz144.

Abstract

Thyroid cancer is one of the common malignancies of the endocrine system and the number of thyroid cancer cases is increasing constantly. Significant work has focused on the molecular mechanisms of thyroid cancer, but many mechanisms remain undiscovered. In this study, we employed a comprehensive analysis of whole-transcriptome resequencing derived from paired papillary thyroid cancer (PTC) and normal thyroid tissues. We performed a massive parallel whole-transcriptome resequencing of matched PTC and normal thyroid tissues in 19 patients and found that integrin subunit alpha 7 (ITGA7) was downregulated in thyroid tumor tissues, but the function of ITGA7 in this cancer is still unclear. We also discovered that ITGA7 gene in thyroid cancer tissues was downregulated compared to paired adjacent non-tumor tissues by real-time quantitative polymerase chain reaction. After transfection with small interfering RNA to knock down ITGA7, the abilities of colony formation, proliferation, migration, and invasion were enhanced in PTC cell lines (TPC1 and KTC-1). Meanwhile, ITGA7 knockdown decreased apoptotic cell death in thyroid cells but promoted the expressions of N-cadherin and vimentin and decreased E-cadherin expression by epithelial-to-mesenchymal transition, which may induce invasion and migration. In conclusion, these results indicated that ITGA7 is involved in the progress of PTC and might act as a tumor suppressor gene.

摘要

甲状腺癌是内分泌系统常见的恶性肿瘤之一,其发病率呈不断上升趋势。目前,研究人员已对甲状腺癌的分子机制进行了大量研究,但仍有许多机制尚未被发现。本研究通过对配对的甲状腺乳头状癌(PTC)和正常甲状腺组织的全转录组重测序进行综合分析,发现整合素亚基α 7(ITGA7)在甲状腺肿瘤组织中呈下调表达,但 ITGA7 在这种癌症中的功能尚不清楚。我们还通过实时定量聚合酶链反应发现,与配对的相邻非肿瘤组织相比,甲状腺癌组织中的 ITGA7 基因表达下调。用小干扰 RNA 转染敲低 ITGA7 后,PTC 细胞系(TPC1 和 KTC-1)的集落形成、增殖、迁移和侵袭能力增强。同时,ITGA7 敲低减少了甲状腺细胞的凋亡性死亡,但通过上皮间质转化促进了 N-钙粘蛋白和波形蛋白的表达,降低了 E-钙粘蛋白的表达,这可能诱导了侵袭和迁移。总之,这些结果表明 ITGA7 参与了 PTC 的进展,可能作为一种肿瘤抑制基因发挥作用。

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