Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University , Wenzhou, Zhejiang, China.
Cancer Biol Ther. 2021 Jan 2;22(1):5-11. doi: 10.1080/15384047.2020.1832429. Epub 2020 Dec 13.
Breast cancer is the most common cancer in women, and triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancer. High mobility group AT-hook 2 (HMGA2) is overexpressed in some tumors and closely associated with patients' prognosis. However, the mechanisms involved in the regulation of HMGA2 in TNBC still remain unclear.
In this study, HMGA2 level in TNBC cell lines was analyzed by western blot. After knockdown of HMGA2 expression by RNA interference in TNBC cell lines MDA-MB-231 and SUM149, wound healing and transwell assays were conducted to examine the effects of HMGA2 on migration and invasion. Tumor metastasis was assessed in amouse xenograft model invivo. Furthermore, expression levels of epithelial-mesenchymal transition (EMT) biomarkers and involvement of the Hippo-YAP pathway were detected by western blot.
Compared to normal breast epithelial cells, the expression levels of HMGA2 were significantly increased in TNBC cell lines (all < .05). Downregulation of HMGA2 dramatically inhibited the migration and invasion of MDA-MB-231 and SUM149 cells (all < .01) invitro, and suppressed the tumor metastasis of nude mice xenograft model invivo. Western blot analysis revealed alterations in EMT biomarkers: the expression of mesenchymal markers N-cadherin, Vimentin and Snail were decreased, while the expression of epithelial marker E-cadherin was increased. Downregulated expression of HMGA2 attenuated Hippo-YAP related protein expression and the stability of YAP.
HMGA2 is highly expressed in TNBC cells. Downregulation of HMGA2 inhibits the migration and invasion of TNBC and invivo tumor metastasis mediated through inhibition of EMT and Hippo-YAP pathway.
乳腺癌是女性最常见的癌症，三阴性乳腺癌（TNBC）约占所有乳腺癌的 15-20%。高迁移率族蛋白 A2（HMGA2）在一些肿瘤中过度表达，与患者的预后密切相关。然而，HMGA2 在 TNBC 中的调控机制尚不清楚。
本研究通过 Western blot 分析了 TNBC 细胞系中 HMGA2 的水平。在 TNBC 细胞系 MDA-MB-231 和 SUM149 中通过 RNA 干扰敲低 HMGA2 表达后，进行划痕愈合和 Transwell 测定，以研究 HMGA2 对迁移和侵袭的影响。在体内小鼠异种移植模型中评估肿瘤转移。此外，通过 Western blot 检测上皮间质转化（EMT）标志物的表达水平和 Hippo-YAP 通路的参与情况。
与正常乳腺上皮细胞相比，TNBC 细胞系中 HMGA2 的表达水平显著升高（均<.05）。HMGA2 下调显著抑制 MDA-MB-231 和 SUM149 细胞的迁移和侵袭（均<.01），并抑制体内裸鼠异种移植模型的肿瘤转移。Western blot 分析显示 EMT 标志物发生改变：间质标志物 N-钙黏蛋白、波形蛋白和 Snail 的表达减少，而上皮标志物 E-钙黏蛋白的表达增加。HMGA2 下调表达减弱了 Hippo-YAP 相关蛋白表达和 YAP 的稳定性。
HMGA2 在 TNBC 细胞中高表达。下调 HMGA2 抑制 TNBC 的迁移和侵袭，并通过抑制 EMT 和 Hippo-YAP 通路抑制体内肿瘤转移。
