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ST7-AS1的过表达通过微小RNA-181b-5p依赖性抑制含三联体基序蛋白3增强甲状腺乳头状癌细胞的凋亡并抑制其增殖。

Overexpression of ST7-AS1 Enhances Apoptosis and Inhibits Proliferation of Papillary Thyroid Carcinoma Cells Via microRNA-181b-5p-Dependent Inhibition Tripartite Motif Containing 3.

作者信息

Zhao Yuan, Feng Xiaoyun, Zhao Yonggang, Yang Huijuan, Zhang Chunjie

机构信息

Department of Pathology, The First People's Hospital of Lianyungang, Lianyungang, 222000, Jiangsu, China.

Department of Pathology, ZhongShan-XuHui Hospital, FuDan University, Shanghai, 200031, China.

出版信息

Mol Biotechnol. 2023 Mar;65(3):477-490. doi: 10.1007/s12033-022-00536-7. Epub 2022 Aug 27.

Abstract

Long non-coding RNAs (lncRNAs) are of great significance in the pathogenesis and progression of papillary thyroid carcinoma (PTC). LncRNA tumorigenicity 7 antisense RNA 1 (ST7-AS1) is a newly identified lncRNA serving as an oncogene or tumor suppressor in different tumors; however, the role of ST7-AS1 in PTC remains completely unknown. In this study, ST7-AS1 was mainly distributed in the cytoplasm of PTC cells and presented reduced expression in THCA tumors and PTC cell lines. Functional experiments revealed that overexpressed ST7-AS1 inhibited the viability and proliferation of PTC cells, whereas accelerated the apoptosis of PTC cells. The expression of miR-181b-5p was upregulated and it bound with ST7-AS1 in PTC cells. Moreover, TRIM3 exhibited downregulated expression level in PTC cells and ST7-AS1 elevated TRIM3 expression via harboring miR-181b-5p. Rescue experiments illuminated that knockdown of TRIM3 reversed ST7-AS1 overexpression-induced promotion on PTC cell proliferation and suppression on PTC cell apoptosis. Overall, overexpression of ST7-AS1 enhances apoptosis and represses proliferation of PTC cells via targeting the miR-181b-5p/TRIM3 axis, which may help broaden the horizon and establish the foundation to develop therapeutic strategies for PTC in the future.

摘要

长链非编码RNA(lncRNAs)在甲状腺乳头状癌(PTC)的发病机制和进展中具有重要意义。LncRNA致瘤性7反义RNA 1(ST7-AS1)是一种新发现的lncRNA,在不同肿瘤中作为癌基因或肿瘤抑制因子发挥作用;然而,ST7-AS1在PTC中的作用仍然完全未知。在本研究中,ST7-AS1主要分布于PTC细胞的细胞质中,且在甲状腺癌(THCA)肿瘤和PTC细胞系中表达降低。功能实验表明,过表达ST7-AS1可抑制PTC细胞的活力和增殖,同时加速PTC细胞的凋亡。miR-181b-5p在PTC细胞中的表达上调,且与ST7-AS1结合。此外,TRIM3在PTC细胞中的表达水平下调,而ST7-AS1通过结合miR-181b-5p上调TRIM3的表达。挽救实验表明,敲低TRIM3可逆转ST7-AS1过表达诱导的PTC细胞增殖促进作用和凋亡抑制作用。总体而言,ST7-AS1的过表达通过靶向miR-181b-5p/TRIM3轴增强PTC细胞的凋亡并抑制其增殖,这可能有助于拓宽视野并为未来开发PTC治疗策略奠定基础。

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