J Cancer 2020; 11(9):2621-2631. doi:10.7150/jca.40171 This issue

Research Paper

ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway

Yi Qu1, Ying He1, Yang Yang1, Shaoqing Li1, Wei An1, Zhilin Li1, Xue Wang1, Zhengxue Han2✉, Lizheng Qin2✉

1. Medical Doctor, Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China, 100050
2. Professor and Medical Doctor, Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China, 100050

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Citation:
Qu Y, He Y, Yang Y, Li S, An W, Li Z, Wang X, Han Z, Qin L. ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway. J Cancer 2020; 11(9):2621-2631. doi:10.7150/jca.40171. Available from https://www.jcancer.org/v11p2621.htm

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Abstract

Objectives: 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.

Materials and methods: 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.

Results: 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.

Conclusion: These data indicate that ALDH3A1 may serve as a biomarker and may be developed into a novel treatment for OSCC.

Keywords: ALDH3A1, oral squamous cell carcinoma, lymph node metastasis, epithelial-mesenchymal transition, prognostic biomarker, IL-6