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长链非编码RNA DLEU2通过介导miR-205-5p/TNFAIP8轴驱动甲状腺癌的恶性行为。

Long noncoding RNA DLEU2 drives the malignant behaviors of thyroid cancer through mediating the miR-205-5p/TNFAIP8 axis.

作者信息

Yang Jiwen, Huang Yayin, Dong Bohan, Dai Yunhai

机构信息

Department of Nuclear Medicine, Yijishan Hospital of Wannan Medical College, Wuhu City, Anhui Province, China.

Department of Clinical Laboratory, The Second People's Hospital of Wuhu, Wuhu City, Anhui Province, China.

出版信息

Endocr Connect. 2021 Apr 26;10(4):471-483. doi: 10.1530/EC-21-0046.

Abstract

OBJECTIVE

Considering the plight in thyroid cancer therapy, we aimed to find novel therapeutic targets from a molecular perspective.

METHODS

Quantitative real-time PCR (qRT-PCR) and Western blot assay were carried out to determine RNA and protein expression. Cell counting kit-8 (CCK8) assay, flow cytometry, transwell migration assay and aerobic glycolysis analysis were performed to analyze cell proliferation, apoptosis, migration and aerobic glycolysis of thyroid cancer cells. MiRcode and Starbase software were used to search the downstream genes of long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 2 (DLEU2) and microRNA-205-5p (miR-205-5p), and the intermolecular combination was confirmed by dual-luciferase reporter assay. The in vivo role of DLEU2 in tumor growth was verified using the murine xenograft model.

RESULTS

DLEU2 and tumor necrosis factor-α-induced protein 8 (TNFAIP8) were highly expressed in thyroid cancer tissues and cell lines. DLEU2 and TNRAIP8 promoted the proliferation, migration and aerobic glycolysis and restrained the apoptosis of thyroid cancer cells. DLEU2/miR-205-5p/TNFAIP8 signaling axis was identified in thyroid cancer cells. TNFAIP8 overexpression largely rescued the malignant phenotypes in DLEU2-silenced thyroid cancer cells. DLEU2 positively regulated TNFAIP8 expression by acting as miR-205-5p sponge in thyroid cancer cells. DLEU2 silencing blocked the growth of xenograft tumors in vivo.

CONCLUSION

lncRNA DLEU2 exerted a pro-tumor role to promote proliferation, migration and aerobic glycolysis while repressing the apoptosis of thyroid cancer cells via miR-205-5p/TNFAIP8 axis.

摘要

目的

鉴于甲状腺癌治疗面临的困境,我们旨在从分子层面寻找新的治疗靶点。

方法

采用定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法检测RNA和蛋白质表达。运用细胞计数试剂盒-8(CCK8)检测、流式细胞术、Transwell迁移实验及有氧糖酵解分析,分析甲状腺癌细胞的增殖、凋亡、迁移及有氧糖酵解情况。利用MiRcode和Starbase软件搜索淋巴细胞白血病2(DLEU2)缺失的长链非编码RNA(lncRNA)和微小RNA-205-5p(miR-205-5p)的下游基因,并通过双荧光素酶报告基因实验证实分子间的结合。使用小鼠异种移植模型验证DLEU2在肿瘤生长中的体内作用。

结果

DLEU2和肿瘤坏死因子-α诱导蛋白8(TNFAIP8)在甲状腺癌组织和细胞系中高表达。DLEU2和TNRAIP8促进甲状腺癌细胞的增殖、迁移及有氧糖酵解,并抑制其凋亡。在甲状腺癌细胞中鉴定出DLEU2/miR-205-5p/TNFAIP8信号轴。TNFAIP8过表达在很大程度上挽救了DLEU2沉默的甲状腺癌细胞中的恶性表型。在甲状腺癌细胞中,DLEU2通过充当miR-205-5p海绵体正向调节TNFAIP8的表达。DLEU2沉默可阻断体内异种移植肿瘤的生长。

结论

lncRNA DLEU2通过miR-205-5p/TNFAIP8轴发挥促肿瘤作用,促进甲状腺癌细胞的增殖、迁移及有氧糖酵解,同时抑制其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3394/8111323/2442b5a7e88c/EC-21-0046fig1.jpg

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