Novel chimeric transcript RRM2-c2orf48 promotes metastasis in nasopharyngeal carcinoma

Abstract

Recently, chimeric transcripts have been found to be associated with the pathogenesis and poor prognosis of malignant tumors. Through our preliminary experiment, a novel chimeric transcript called chimeric transcript RRM2-c2orf48 was detected in C666-1, a classical cell line of human nasopharyngeal carcinoma (NPC). Therefore, the objective of this study was to demonstrate the existence and expression of novel chimeric transcript RRM2-c2orf48 and to explore the main functions and mechanisms of RRM2-c2orf48 in NPC. In this study, the expression of RRM2-c2orf48 was evaluated in NPC cells and specimens. Effects of RRM2-c2orf48 on migration and invasive capacities were detected in vivo and vitro. Moreover, ways in which RRM2-c2orf48 increases the invasive capacities of NPC were explored. As a result, the presence of novel chimeric transcript RRM2-c2orf48 was confirmed in C666-1 by RT-PCR and sequencing, and it was a read-through between RRM2 and c2orf48 through the transcription of interchromosome. Higher expressions of novel RRM2-c2orf48 were detected in NPC cell lines and NPC tissue specimens relative to the controls and its expression was be statistically relevant to TNM staging. High level of RRM2-c2orf48 could increase the migration and invasive capacities of NPC cells, potentially as a result of NPC cell epithelial–mesenchymal transition. RRM2-c2orf48 could also enhance resistance of chemotherapy. In vivo, RRM2-c2orf48 could enhance lung and lymph node metastasis in nude mice. These results demonstrate that high levels of RRM2-c2orf48 expression may be a useful predictor of NPC patients of metastatic potency, presenting potential implications for NPC diagnosis and therapy.

NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma

“…Immunofluorescence analysis was performed as described previously [23]. The samples were incubated overnight at 4 °C with primary antibodies.…”

Construction of a Competitive Endogenous RNA Network in Uterine Corpus Endometrial Carcinoma

“…Li et al constructed a ceRNA regulatory network for oral squamous cell carcinoma, and showed that 6 lncRNAs, including C2orf48, were associated with overall cancer survival [30]. Another study showed that C2orf48 could bind to RRM2 to form a chimeric transcript and high expression of RRM2-C2orf48 increased migration and invasion of nasopharyngeal carcinoma cells [31]. The role of C2orf48 in endometrial carcinoma has not been characterized.…”

Potential mechanism of RRM2 for promoting Cervical Cancer based on weighted gene co-expression network analysis

“…International Publisher adrenocortical cancer [8], lung cancer [9], nasopharyngeal cancer [10], gastric cancer [11] and neuroblastoma [12], as well as being a predictor of poor prognosis [13][14][15][16][17]. Our previous study had indicated that RRM2 plays a critical role in the diagnosis and treatment of cervical cancer [18].…”

“…RRM2, as a component of ribonucleotide reductase (RNR), plays vital roles in many critical cellular processes such as cell proliferation, invasiveness, migration, angiogenesis and senescence 7 . It is frequently overexpressed and serves as an oncogene in various malignancies, including adrenocortical cancer 8 , lung cancer 9 , nasopharyngeal cancer 10 , gastric cancer 11 and neuroblastoma 12 , as well as being a predictor of poor prognosis 13 - 17 . Our previous study had indicated that RRM2 plays a critical role in the diagnosis and treatment of cervical cancer 18 .…”