Coiled-coil domain-containing protein-124 (Ccdc124) is a novel RNA binding factor up-regulated in endometrial, ovarian, and urinary bladder cancers

Abstract

BACKGROUND: Coiled-coil domain containing protein-124 (Ccdc124) is a putative mRNA-binding factor associated with cell division, and ribosome biology. Previous reports mentioned an up-regulation of CCDC124 gene in cancer, and listed its mRNA in a molecular prognostic signature in breast cancer. OBJECTIVES: Establishing RNA-binding characteristics of Ccdc124 for a better molecular functional characterization, and carrying-out retrospective studies in order to evaluate its aberrant expression in human cancer samples from various tissue origins. METHODS: Bioinformatics calculations followed by RIP and RNA-seq experiments were performed to investigate mRNA targets of Ccdc124. Quantitative studies on arrays of cDNAs from different cancers and IHC assays on tissue arrays were used to assess CCDC124 expression levels in cancers. RESULTS: Ccdc124 was characterized as an RNA-binding protein (RBP) interacting with various mRNAs. CCDC124 mRNA levels were high in tumors, with a particular up-regulation in cancers from esophagus, adrenal gland, endometrium, liver, ovary, thyroid, and urinary bladder. IHC assays indicated strong Ccdc124 positivity in endometrial (95.4%), urinary bladder (68.4%), and ovarian cancers (86.8%). CONCLUSION: Ccdc124 is a cytokinesis related RBP interacting with various mRNAs. CCDC124 mRNA over-expression and an accompanied increase in Ccdc124 protein accumulation was reported in cancers, indicating this RBP as a novel cancer cell marker.

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases

“…Further study found that six CEGs, including CCDC124, NR2C2AP, SLC25A39, DDX49, KXD1, TXNL4A, had good diagnostic value and were related to poor OS in HCC patients (all AUC>0.90; all HR > 1.40, p < 0.05). According to the previous reports, CCDC124 was significantly overexpressed in endometrial cancer (EC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), and ovarian cancer (OC) was related to tumor cell division, tumor heterogeneity and drug resistance ( Lu et al, 2020 ; Arslan et al, 2021 ). The expression of DDX49 was significantly up-regulated in HCC, and knocking it down could suppress the growth and metastasis of HCC tumors, while overexpression of DDX49 could enhance the above procession ( Dai et al, 2021 ).…”

RNA-binding proteins in ovarian cancer: a novel avenue of their roles in diagnosis and treatment

“…Coiled-Coil Domain Containing protein-124 (Ccdc124) is an mRNA-binding factor related to cell division and ribosome biology. Upregulated Ccdc124 expression was associated with a prolonged prognosis in OC patients [ 79 ].…”

Proteomics analysis identifies the ribosome associated coiled‐coil domain‐containing protein‐124 as a novel interaction partner of nucleophosmin‐1

“…The strict conservation of the CCDC124 gene in all eukaryotes (https://www.orthodb.org; Telkoparan et al., 2013; Arslan et al., 2021) indicates the important role of the encoded protein. The coiled‐coil‐domain‐containing protein‐124 (Ccdc124) is an RNA‐binding protein containing putative intrinsically disordered regions at its N‐ and C‐termini (Arslan et al., 2021).…”

“…The strict conservation of the CCDC124 gene in all eukaryotes (https://www.orthodb.org; Telkoparan et al., 2013; Arslan et al., 2021) indicates the important role of the encoded protein. The coiled‐coil‐domain‐containing protein‐124 (Ccdc124) is an RNA‐binding protein containing putative intrinsically disordered regions at its N‐ and C‐termini (Arslan et al., 2021). The orthologue of CCDC124 gene in Saccharomyces cerevisiae , the late‐annotated short open reading frame‐2 ( LSO2 ), encodes a protein that localizes in the ribosome and interacts with the ribosomal 25S RNA in a region near the A site of the ribosome (Wang et al., 2018).…”

“…Firstly, the size and domain compositions of the two proteins are largely different, and indeed Lso2 protein is an outlier even among its orthologues in other lower eukaryotic organisms: Lso2 is composed of 92 amino acid (a.a.) residues (∼10.5 kDa, Wang et al., 2018), which approximately corresponds only to the N‐terminus half of its human counterpart (Ccdc124 protein, 223 a.a. residues; ∼32 kDa, Telkoparan et al., 2013), or to that of plant and evolutionarily very close fungal orthologues (AtOxs1 in Arabidopsis thaliana , 234 a.a.; Oxs1 in the fission yeast Schizosaccharomyces pombe, 207 a.a.; NcOxs1 in the filamentous fungi Neurospora crassa , 224 a.a.; He et al., 2017). Related to the important molecular size difference, the domain composition of the S. cerevisiae Lso2 protein is largely missing the mid‐region/C‐terminus localized RNA‐binding domains and intrinsically disordered regions (IDRs) that were present in all other orthologues including Ccdc124 (RBD; Arslan et al., 2021). Secondly, the entire cellular population of yeast Lso2 seems to be ribosome‐associated, while the majority of Ccdc124 in human cells are in the nonribosomal pool, with only a minority being enriched in the hibernating monosome fraction (Wang et al., 2018).…”