Ovarian cancer (OC) is the second most common cause of death from gynecological tumors in women worldwide, inferior to cervical cancer [1]. Since 1995, the 5-year overall survival rate of OC patients has not seen a significant improvement, only remaining at about 48 % [2]. Consequently, it is essential to find new tumor indicators and targets in order to improve the prognosis of OC patients.
Protein regulator of cytokinesis 1 (PRC1) consists of 620 amino acids with a molecular size of 72 kDa [3]. PRC1, a protein associated with microtubules, interacts with microtubules and significantly contributes to the preservation of spindle integrity in mammalian cells during late mitosis [4,5]. Apart from its primary role in mitosis, PRC1 was also involved in the development of human tumors. It has been suggested that PRC1 is highly expressed in diverse types of tumors and promoted the development of cancers, encompassing breast carcinoma [6], hepatocellular carcinoma [7] and prostate cancer [8]. However, the possible carcinogenic role and molecular mechanism of PRC1 in OC have not been fully elucidated.
Ribosomes, consisting of approximately 80 ribosomal proteins (RPs) and ribosomal RNAs (rRNAs), is vitally important to the protein synthesis [9]. The activation of p53, a tumor suppressor protein, is a consequence of ribosomal stress [10]. As a transcription factor, p53 can regulate a great deal of genes related to cancer prevention and suppression by obstructing the replication of damaged DNA or altering cell proliferation [11]. Mouse Double Minute 2 (MDM2), an E3 ubiquitin ligase, regulates p53 by binding to it and inducing its ubiquitination-dependent degradation [12]. Ribosomal Protein L4 (RPL4), is a constituent of the 60S subunit of ribosome. Earlier studies have demonstrated RPL4's ability to engage with MDM2 in segregating its E3 ligase function, thus maintaining and activating p53, suggesting that the RPL4-MDM2-p53 pathway is capable of reacting to ribosomal stress and functioning as a tumor inhibitor [13].
In this study, by analyzing multiple bioinformatics databases and clinical histology, we demonstrated that compared to normal ovarian epithelium, PRC1 was expressed more highly in ovarian malignancies. Subsequently, we showcased that the suppressive influence of PRC1 on p53 activity and its role as a controller of the RPL4-MDM2-p53 axis, which functionally contributed to oncogenesis and progression of OC. Our research may shed light on the part PRC1 plays in advancing OC growth.
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