Zhang H, Tang Z, Deng C, He Y, Wu F, Liu O, Hu C
Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Oral and Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, China.
Oral Dis. 2017 Mar;23(2):255-264. doi: 10.1111/odi.12608. Epub 2016 Dec 23.
To analyze the effects of HMGA2 on proliferation, invasion, and metastasis in tongue squamous cell carcinoma (TSCC).
HMGA2 knockdown was performed in SCC15 cell lines, and functional assay was applied to observe the effects on cell migration and invasion. Real-time PCR, Western blotting, and immunohistochemistry (IHC) were also used to measure the expression of HMGA2 and EMT markers.
HMGA2 expression was decreased after lentivirus infection. Functional assay showed that silence of HMGA2 can inhibit the proliferation of SCC15 cells and arrest the cells in G1/S phase. Moreover, knockdown of HMGA2 enhanced apoptosis of SCC15 cells. Wound-healing assay and transwell assay indicated that knockdown of HMGA2 significantly inhibited migration and invasion ability of SCC15 cells. Expression detection suggested that HMGA2 may be involved in the metastasis of SCC15 cells by activating Twist family expression and inducing epithelial-mesenchymal transition (EMT) process. IHC analysis showed that HMGA2 and vimentin were up-regulated in TSCC tissues, while E-cadherin was down-regulated. Clinicopathological analysis indicated that expression of HMGA2, E-cadherin, and Vimentin were associated with recurrence of patients with TSCC.
Our findings demonstrated that HMGA2 may promote malignant transformation of TSCC through EMT process and may be an independent prognosis biomarker for TSCC.
分析HMGA2对舌鳞状细胞癌（TSCC）增殖、侵袭和转移的影响。
在SCC15细胞系中进行HMGA2基因敲低，并应用功能测定法观察其对细胞迁移和侵袭的影响。还采用实时定量聚合酶链反应（Real-time PCR）、蛋白质免疫印迹法（Western blotting）和免疫组织化学（IHC）检测HMGA2及上皮-间质转化（EMT）标志物的表达。
慢病毒感染后HMGA2表达降低。功能测定显示，HMGA2沉默可抑制SCC15细胞增殖并使细胞停滞于G1/S期。此外，HMGA2基因敲低增强了SCC15细胞的凋亡。伤口愈合试验和Transwell试验表明，HMGA2基因敲低显著抑制了SCC15细胞的迁移和侵袭能力。表达检测提示，HMGA2可能通过激活Twist家族表达并诱导上皮-间质转化（EMT）过程参与SCC15细胞的转移。免疫组织化学分析显示，HMGA2和波形蛋白在TSCC组织中上调，而E-钙黏蛋白下调。临床病理分析表明，HMGA2、E-钙黏蛋白和波形蛋白的表达与TSCC患者的复发相关。
我们的研究结果表明，HMGA2可能通过EMT过程促进TSCC的恶性转化，并且可能是TSCC的一个独立预后生物标志物。
