Qu Yi, He Ying, Yang Yang, Li Shaoqing, An Wei, Li Zhilin, Wang Xue, Han Zhengxue, Qin Lizheng
Medical Doctor, Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China, 100050.
Professor and Medical Doctor, Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China, 100050.
J Cancer. 2020 Feb 19;11(9):2621-2631. doi: 10.7150/jca.40171. eCollection 2020.
Aldehyde dehydrogenase 3A1 (ALDH3A1) is a member of the ALDH superfamily and its relationship with oral squamous cell carcinoma (OSCC) still unknown. In our subject, we aimed to reveal the expression pattern and clinical value of ALDH3A1 in OSCC and its biological function in OSCC cell lines. The expression level of ALDH3A1 in paired OSCC tissues and adjacent noncancerous tissues were detected by quantitative real-time PCR, Western blot and immunohistochemistry. The relationship between ALDH3A1 expression and clinical characteristics was analyzed. Besides, cell-counting kit 8, colony formation, wound healing, transwell invasion, apoptosis and cell cycle assays were employed to assess the role of ALDH3A1 in OSCC cells. To explore the influence of ALDH3A1 on OSCC epithelial-to-mesenchymal transition (EMT), the expression of EMT markers (E-cadherin, vimentin, snail, MMP3) on OSCC cells were detected, and possible mechanisms were analyzed. In OSCC tissues, ALDH3A1 was significantly decreased compared to the adjacent normal tissues. Lower ALDH3A1 expression in OSCC tissues was associated with a higher incidence of lymph node metastasis (LNM). Moreover, the overall survival of OSCC with low ALDH3A1 expression was significantly worse compared to that of OSCC with high ALDH3A1 expression. Restored expression of ALDH3A1 suppressed cell proliferation, migration and invasion in OSCC cells. Further experiments showed that ALDH3A1 might inhibit EMT in OSCC via a regulation of the IL-6/STAT3 signal pathway. These data indicate that ALDH3A1 may serve as a biomarker and may be developed into a novel treatment for OSCC.
醛脱氢酶3A1（ALDH3A1）是ALDH超家族的成员，其与口腔鳞状细胞癌（OSCC）的关系尚不清楚。在本研究中，我们旨在揭示ALDH3A1在OSCC中的表达模式、临床价值及其在OSCC细胞系中的生物学功能。通过定量实时PCR、蛋白质免疫印迹和免疫组织化学检测配对的OSCC组织和相邻正常组织中ALDH3A1的表达水平。分析ALDH3A1表达与临床特征之间的关系。此外，采用细胞计数试剂盒8、集落形成、伤口愈合、Transwell侵袭、凋亡和细胞周期检测来评估ALDH3A1在OSCC细胞中的作用。为了探讨ALDH3A1对OSCC上皮-间质转化（EMT）的影响，检测OSCC细胞中EMT标志物（E-钙黏蛋白、波形蛋白、蜗牛蛋白、基质金属蛋白酶3）的表达，并分析可能的机制。在OSCC组织中，与相邻正常组织相比，ALDH3A1显著降低。OSCC组织中ALDH3A1表达较低与淋巴结转移（LNM）发生率较高相关。此外，与高ALDH3A1表达的OSCC相比，低ALDH3A1表达的OSCC的总生存期明显更差。恢复ALDH3A1的表达可抑制OSCC细胞的增殖、迁移和侵袭。进一步实验表明ALDH3A1可能通过调节IL-6/STAT3信号通路抑制OSCC中的EMT。这些数据表明ALDH3A可能作为一种生物标志物，并且可能发展成为OSCC的一种新型治疗方法。
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