Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma.

Xiuying Sun, Jinhui Zhou, Zhicun Zhang

Bioengineered 2022 Apr

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Targeted therapy is an important therapeutic strategy currently, however, the development of targeted therapy for nasopharyngeal carcinoma (NPC) is relatively lagging. Cullin 4A (CUL4A) was reported to be overexpressed in NPC; nevertheless, the specific role of CUL4A remains unrevealed. NPC cells and tumor-bearing mice were cultivated to explore the role and mechanism of CUL4A in NPC. After evaluating CUL4A levels in NPC cells, functional experiments were carried out to investigate the effects of CUL4A knockdown and overexpression on cell proliferative, invasive and migratory aptitude as well as NF-κB signaling. Following the GeneMANIA database predicted that protein arginine methyltransferase 5 (PRMT5) was downstream of CUL4A, the mediated role of PRMT5 in the regulation of CUL4A on cells was then determined. Moreover, the tumor volumes and weights of tumor-bearing mice were recorded, and the levels of proliferation-, migration-, and NF-κB signaling-related proteins in the tumor were determined. Herein, CUL4A was enhanced in NPC cells, and its knockdown and overexpression separately suppressed and promoted cell proliferative, invasive, and migratory aptitude as well as NF-κB signal activation. Novelty, PRMT5 knockdown reversed the influences of CUL4A overexpression on these aspects. In addition, its knockdown likewise reversed the facilitating impact of CUL4A expression on tumor growth and declined the expression levels of proliferation-, migration-, and NF-κB signaling-related protein in the tumor. Together, this paper indicated that CUL4A promoted the proliferative, invasive, and migratory aptitude of NPC cells as well as tumor growth by promoting PRMT5 to activate NF-κB signaling.

Citation

Xiuying Sun, Jinhui Zhou, Zhicun Zhang. Cullin 4A/protein arginine methyltransferase 5 (CUL4A/PRMT5) promotes cell malignant phenotypes and tumor growth in nasopharyngeal carcinoma. Bioengineered. 2022 Apr;13(4):8712-8723