Dong Yi, Wang Gangle
Department of Breast, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing 100006, China.
Int J Clin Exp Pathol. 2020 Mar 1;13(3):393-402. eCollection 2020.
Breast cancer (BC) is a common cancer with high incidence in women worldwide. Although there are some studies focusing on the pathogenesis of BC, the regulatory mechanism needs to be further investigated. The function of lncRNA and miRNA has been demonstrated to participate in cell progression of BC. However, the function of SNHG12 has not been clearly elucidated.
We detected the expression of SNHG12 and miR-451a using quantitative real-time PCR (qRT-PCR). The protein expression of AKT, p-AKT, mTOR and p-mTOR were measured using western blot. The relationship between SNHG12 and miR-451a was confirmed by luciferase reporter assay. Cell proliferation was measured using MTT assay. Transwell assay was used to detect cell migration and invasion. Xenograft transplantation was used to detect the function of SNHG12 in vivo.
In this study, we found that SNHG12 was significantly increased in BC tissues and cells. Knockdown of SNHG12 inhibited BC cell proliferation, invasion, and migration in vitro as well as suppressed tumor growth in vivo. In addition, miR-451a expression was obviously down-regulated in BC tissues and had negative correlation with SNHG12. Luciferase reporter assay determined that miR-451a was a target miRNA of SNHG12. Notably, SNHG12 knockdown decreased cell proliferation, migration, invasion, and AKT/mTOR pathway activation which could be reversed by down-regulation of miR-451a.
Knockdown of SNHG12 inhibited cell proliferation, invasion, and migration by regulating miR-451a through suppression of AKT/mTOR pathway in BC.
乳腺癌（BC）是一种在全球女性中发病率很高的常见癌症。尽管有一些研究聚焦于BC的发病机制，但调控机制仍需进一步研究。长链非编码RNA（lncRNA）和微小RNA（miRNA）的功能已被证明参与了BC的细胞进展。然而，SNHG12的功能尚未得到明确阐明。
我们使用定量实时聚合酶链反应（qRT-PCR）检测SNHG12和miR-451a的表达。使用蛋白质免疫印迹法检测AKT、磷酸化AKT（p-AKT）、哺乳动物雷帕霉素靶蛋白（mTOR）和磷酸化mTOR（p-mTOR）的蛋白表达。通过荧光素酶报告基因检测法确认SNHG12与miR-451a之间的关系。使用MTT法检测细胞增殖。采用Transwell实验检测细胞迁移和侵袭。通过异种移植实验检测SNHG12在体内的功能。
在本研究中，我们发现SNHG12在BC组织和细胞中显著上调。敲低SNHG12可抑制BC细胞在体外的增殖、侵袭和迁移，并在体内抑制肿瘤生长。此外，miR-451a在BC组织中的表达明显下调，且与SNHG12呈负相关。荧光素酶报告基因检测法确定miR-451a是SNHG12的靶标miRNA。值得注意的是，敲低SNHG12可降低细胞增殖、迁移、侵袭以及AKT/mTOR信号通路的激活，而miR-451a的下调可逆转这种作用。
在BC中，敲低SNHG12通过抑制AKT/mTOR信号通路调控miR-451a，从而抑制细胞增殖、侵袭和迁移。
