Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma.

Mingjie Zhang, Han Lin, Xiaohan Ge, Yue Xu

Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 2021 May

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Invasion and metastasis are major challenges in the treatment of oral cancer. We hypothesize that cleavage and polyadenylation specific factor 4 (CPSF4), a key mediator of cell growth and metastasis in several types of cancers, contributes to oral squamous cell carcinoma (OSCC) pathogenesis. The expression and production of CPSF4 in OSCC cell lines and tumor tissues were assessed by RT-PCR and western blot, respectively. The relationships between CPSF4 production and OSCC clinicopathological features were analyzed using immunohistochemistry. The effects of CPSF4 on viability, proliferation, migration, invasion, cell cycle distribution, and apoptosis of OSCC cells were measured by MTS assay, colony formation assay, wound-healing, transwell invasion assay, flow cytometry, and cell apoptosis assay, respectively. Western blot analysis was used to assess alteration of PI3K-AKT pathway member levels in cell lines transfected with CPSF4 siRNA. Mice xenograft models were used to determine the effect of CPSF4 on OSCC tumor growth in vivo. CPSF4 was highly expressed in OSCC cell lines and tumor tissues compared with adjacent normal oral tissues. High CPSF4 expression was strongly correlated with vascular invasion (P = .004), distant metastasis (P = .001), and TNM stages (P = .001). Moreover, reduction of CPSF4 levels contributed to the inhibition of cell viability, proliferation, invasion and migration, and the induction of apoptosis in OSCC cell lines. Reduction of CPSF4 levels results in OSCC cell cycle arrest in G1 phase by targeting c-Myc. CPSF4 contributed to proliferation inhibition via PI3K-AKT signaling pathway. Reduction of CPSF4 levels inhibits OSCC tumor growth in vivo. Our results suggest that CPSF4 supports OSCC invasion and metastasis and may be a promising therapeutic target for OSCC. Copyright © 2021 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Citation

Mingjie Zhang, Han Lin, Xiaohan Ge, Yue Xu. Overproduced CPSF4 Promotes Cell Proliferation and Invasion via PI3K-AKT Signaling Pathway in Oral Squamous Cell Carcinoma. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2021 May;79(5):1177.e1-1177.e14