Zhao Yuan, Feng Xiaoyun, Zhao Yonggang, Yang Huijuan, Zhang Chunjie
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.
Mol Biotechnol. 2023 Mar;65(3):477-490. doi: 10.1007/s12033-022-00536-7. Epub 2022 Aug 27.
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.
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。