促进甲状腺癌的进展，加速 G1/S 期过渡并抑制细胞凋亡。
Promotes the Progression of Thyroid Cancer by Accelerating G1/S Transition and Inhibiting Apoptosis.
机构信息
Department of Surgical Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang, China.
Department of Operating Theatre, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
出版信息
Dis Markers. 2022 Aug 3;2022:2562595. doi: 10.1155/2022/2562595. eCollection 2022.
BACKGROUND
Thyroid carcinoma (TC) is an increasingly common malignancy of endocrine organs, and its most frequently encountered histotype is papillary thyroid cancer (PTC). Identifying new potential gene alterations is important for completely elucidating the mechanism of PTC initiation and progression. Thus, we performed whole transcriptome sequence analysis (RNA-seq) on 79 PTC tissue samples and paired adjacent nontumor tissue samples to study the molecular mechanism of TC tumorigenesis and progression further. The results of RNA-seq analysis showed that spectrin beta, nonerythrocytic 2 (), was markedly overexpressed in PTC tissues relative to that in the paired nontumor tissues. Additionally, the analysis results for 502 PTC samples and 58 nontumor thyroid samples from The Cancer Genome Atlas dataset were consistent with our RNA-seq results. However, the molecular mechanisms and function of in TC progression remain unknown.
METHODS
We examined gene expression in 48 papillary thyroid tumor tissues and paired adjacent normal thyroid tissues by using qRT-PCR. expression in the TC cell lines was silenced by small interfering RNA. Then, the transfected TC cells were used to investigate the in vitro function of .
RESULT
The expression of was significantly upregulated in our RNA-seq cohort, our local validated cohort, and TCGA RNA-seq cohort. The results of the in vitro experiment revealed that in TC cell lines, downregulation considerably suppressed tumor cell proliferation, the cell cycle, migration, colony formation, and invasion and induced cell apoptosis. Furthermore, the protein levels of CCNE2, CDK2, CDK4, and Bcl-2 were downregulated, and those of P21, Bax, cleaved caspase-8, and cleaved caspase-3 had increased in transfected TC cells relative to in control TC cells.
CONCLUSION
The downregulation of caused apoptosis and retarded G1/S cell cycle transition in TC cells. Thus, may be a good candidate gene for TC diagnosis and therapy.
背景
甲状腺癌（TC）是内分泌器官中一种日益常见的恶性肿瘤，其最常见的组织学类型是甲状腺乳头状癌（PTC）。确定新的潜在基因改变对于完全阐明 PTC 发生和进展的机制非常重要。因此，我们对 79 例 PTC 组织样本和配对的相邻非肿瘤组织样本进行了全转录组序列分析（RNA-seq），以进一步研究 TC 肿瘤发生和进展的分子机制。RNA-seq 分析的结果表明， spectrin beta, nonerythrocytic 2 ( ) 在 PTC 组织中相对于配对的非肿瘤组织明显过表达。此外，来自癌症基因组图谱数据集的 502 例 PTC 样本和 58 例非肿瘤甲状腺样本的分析结果与我们的 RNA-seq 结果一致。然而， 在 TC 进展中的分子机制和功能仍然未知。
方法
我们使用 qRT-PCR 检测了 48 例甲状腺乳头状瘤组织和配对的相邻正常甲状腺组织中的 基因表达。用小干扰 RNA 沉默 TC 细胞系中的 表达。然后，用转染的 TC 细胞来研究 的体外功能。
结果
在我们的 RNA-seq 队列、我们的本地验证队列和 TCGA RNA-seq 队列中， 的表达均显著上调。体外实验的结果表明，在 TC 细胞系中， 下调显著抑制肿瘤细胞增殖、细胞周期、迁移、集落形成和侵袭，并诱导细胞凋亡。此外，转染的 TC 细胞中 CCNE2、CDK2、CDK4 和 Bcl-2 的蛋白水平下调，而 Bax、cleaved caspase-8 和 cleaved caspase-3 的蛋白水平上调。
结论
下调导致 TC 细胞凋亡和 G1/S 细胞周期阻滞。因此， 可能是 TC 诊断和治疗的一个良好候选基因。
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