Knockdown of RFC4 inhibits the cell proliferation of nasopharyngeal carcinoma in vitro and in vivo

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.

Keywords

nasopharyngeal carcinoma / WGCNA / RFC4 / proliferation

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (Nos. 2022YFA1103900 and 2020YFC2002705), the National Natural Science Foundation of China (Nos. 82260715, 82073092, and 82273076), the Guangxi Natural Science Foundation (Nos. 2017GXNSFBA198240, 2018GXNSFAA050055, and 2021GXNSFAA075038), Youth Fund Project of Natural Science Research Project of Guangxi University of Traditional Chinese Medicine (No. 2016QN007), Guangxi Collaborative Innovation Center for Research on Functional Ingredients of Agricultural Residues (No. CICAR2016-P6), and the CAMS Innovation Fund for Medical Sciences (CIFMS; 2021-RC310-003, 2021-I2M-1-014).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-022-0938-x and is accessible for authorized users.

Compliance with ethics guidelines

Shuzhen Guan, Lin Feng, Jinrui Wei, Guizhen Wang, and Lichuan Wu declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 as revised in 2000. Informed consent was obtained from all patients for being included in the study.

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