URG4 expression is a novel prognostic factor for the progression of nasopharyngeal carcinoma and overall survival of patient.
ABSTRACT: URG4, a novel oncogene, is involved in the development and progression of various tumors. This study investigated the clinicopathological significance of URG4 in nasopharyngeal carcinoma (NPC). We used five NPC tissues and adjacent normal nasopharyngeal tissues to determine URG4 expression and found that URG4 was upregulated in NPC tissues. Immunohistochemistry analysis found URG4 was expressed positively in 97.1% (99/102) of NPC samples and highly expressed in 41.2% (42/102) of NPC samples. Its level was positively correlated with advancing clinical stage. Kaplan-Meier analysis with the log-rank test found that patients with high URG4 expression had poor outcome and patients with low URG4 expression had better survival. Statistical analysis showed that there was a significant correlation between URG4 expression and clinical stage, larger tumor size, and lymph node involvement. Cox-regression analysis showed that URG4 expression could serve as a prognostic factor for NPC patients. In summary, this study showed that URG4 was upregulated in NPC tissues, patients with high URG4 expression had poor outcome, and URG4 was found to be a valuable biomarker for NPC progression.
Project description:Cisplatin is a well-known chemotherapeutic agent, it could cause DNA damage and induce apoptotic cell death, but the cisplatin resistance also appears, it's important to reveal the mechanisms of cisplatin resistance . URGCP/URG4 is overexpressed in various tumors and plays critical role during tumor development. We found URGCP/URG4 was upregulated in bladder cancer cells and tissues, URGCP/URG4 overexpression increased the resistance to cisplatin-induced apoptosis in bladder cancer, and promoted anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and downregulated Caspase-3 expression, Knockdown of URGCP/URG4 decreased the resistance to cisplatin-induced apoptosis, and inhibited anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and upregulated Caspase-3 expression. Mechanism analysis found URGCP/URG4 activated NF-?B pathway which is a well-known anti-apoptotic pathway and promoted the expression of NF-?B targeted genes. So we speculated URGCP/URG4 regulates cisplatin-induced apoptosis by activating NF-?B pathway. We also analyzed the correlation between URGCP/URG4 expression and clinical clinicopathologic, and found its expression was positively correlated with bladder cancer progression, it can serve as a valuable prognostic factor. In summary, URGCP/URG4 promotes the resistance to cisplatin-induced apoptosis by activating NF-?B pathway, and is an unfavorable prognostic factor for bladder cancer.
Project description:BACKGROUND: Our recent cDNA microarray data showed that centromere protein F (CENP-F) is significantly upregulated in primary cultured nasopharyngeal carcinoma (NPC) tumor cells compared with normal nasopharyngeal epithelial cells. The goal of this study was to further investigate the levels of CENP-F expression in NPC cell lines and tissues to clarify the clinical significance of CENP-F expression in NPC as well as the potential therapeutic implications of CENP-F expression. METHODS: Real-time RT-PCR and western blotting were used to examine CENP-F expression levels in normal primary nasopharyngeal epithelial cells (NPEC), immortalized nasopharyngeal epithelial cells and NPC cell lines. Levels of CENP-F mRNA were determined by real-time RT-PCR in 23 freshly frozen nasopharyngeal biopsy tissues, and CENP-F protein levels were detected by immunohistochemistry in paraffin sections of 202 archival NPC tissues. Statistical analyses were applied to test for prognostic associations. The cytotoxicities of CENP-F potential target chemicals, zoledronic acid (ZOL) and FTI-277 alone, or in combination with cisplatin, in NPC cells were determined by the MTT assay. RESULTS: The levels of CENP-F mRNA and protein were higher in NPC cell lines than in normal and immortalized NPECs. CENP-F mRNA level was upregulated in nasopharyngeal carcinoma biopsy tissues compared with noncancerous tissues. By immunohistochemical analysis, CENP-F was highly expressed in 98 (48.5%) of 202 NPC tissues. Statistical analysis showed that high expression of CENP-F was positively correlated with T classification (P < 0.001), clinical stage (P < 0.001), skull-base invasion (P < 0.001) and distant metastasis (P = 0.012) inversely correlated with the overall survival time in NPC patients. Multivariate analysis showed that CENP-F expression was an independent prognostic indicator for the survival of the patient. Moreover, we found that ZOL or FTI-277 could significantly enhance the chemotherapeutic sensitivity of NPC cell lines (HONE1 and 6-10B) with high CENP-F expression to cisplatin, although ZOL or FTI-277 alone only exhibited a minor inhibitory effect to NPC cells. CONCLUSION: Our data suggest that CENP-F protein is a valuable marker of NPC progression, and CENP-F expression is associated with poor overall survival of patients. In addition, our data indicate a potential benefit of combining ZOL or FTI-277 with cisplatin in NPC suggesting that CENP-F expression may have therapeutic implications.
Project description:BACKGROUND: Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients. METHODS: URG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors. RESULTS: URG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients. CONCLUSIONS: Our results demonstrated that elevated URG4 protein expression is associated with a poor outcome in patients with early-stage cervical cancer. URG4 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.
Project description:To explore differentially expressed genes between nasopharyngeal carcinoma (NPC) primary tumors and non-cancerous nasopharyngeal tissues, 18 NPC tissue samples versus 18 control samples were utilized to perform genome-wide expressing profiling. Consequently, 2992 genes were found to be differentially expressed in NPC tissues relative to the control (FC>2, P<0.05). Among these 2992 genes, uPA was ranked as the top one in all upregulated genes sorted by ascending order of P-value. Moreover, expression of uPAR was also upregulated in NPC tissues with FC=3.34 and P=7.52×105. 18 nasopharyngeal carcinoma primary tumors and 18 non-cancerous nasopharyngeal tissues were used to perform genome-wide expressing profiling. The median ages of patients were 46 (range, 19-77) for NPC patients and 45 (range, 18-78) for the non-cancerous cohort. Almost one third of patients were female. All samples were collected before any anti-cancer treatment.
Project description:HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.
Project description:Accumulating evidences highlight the critical roles of long noncoding RNAs (lncRNAs) in a variety of cancers. LncRNA PXN-AS1-L was previously shown to exert oncogenic roles in hepatocellular carcinoma. However, the expression, role, and molecular mechanism of PXN-AS1-L in nasopharyngeal carcinoma (NPC) malignancy remain unknown. Here, we determined that PXN-AS1-L is upregulated in NPC tissues and cell lines. Increased expression of PXN-AS1-L predicts worse prognosis of NPC patients. PXN-AS1-L overexpression promotes NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. PXN-AS1-L silencing suppresses NPC cell proliferation, migration, and invasion in vitro. Mechanistically, PXN-AS1-L directly interacts with SAPCD2 mRNA 3'-untranslated region, prevents the binding of microRNAs-AGO silencing complex to SAPCD2 mRNA, and upregulates the mRNA and protein level of SAPCD2. SAPCD2 is also increased in NPC tissues. The expression of SAPCD2 is significantly positively associated with that of PXN-AS1-L in NPC tissues. Gain-of-function and loss-of-function experiments demonstrated that SAPCD2 also promotes NPC cell proliferation, migration, and invasion. Furthermore, depletion of SAPCD2 significantly reverses the roles of PXN-AS1-L in promoting NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. In conclusion, lncRNA PXN-AS1-L is upregulated in NPC and promoted NPC malignancy by upregulating SAPCD2 via direct RNA-RNA interaction.
Project description:<h4>Background</h4>Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC) tissues and its clinicopathologic/prognostic implication are poorly understood.<h4>Methods</h4>In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting (WB) and immunohistochemistry (IHC) in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC) curve analysis, spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model.<h4>Results</h4>Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7%) of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P < 0.05). In univariate survival analysis, overexpression of p300 was found to be an indicator of progression-free (P = 0.002) and overall survival (P = 0.001) in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036).<h4>Conclusions</h4>Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.
Project description:MiR-125b is aberrantly expressed and has a role in the various types of tumors. However, the role and mechanism of miR-125b in nasopharyngeal carcinoma (NPC) are unclear. In this study, we investigated the role and mechanism of miR-125b in NPC. We observed that miR-125b was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM), and its increment was correlated with poor patient survival, and was an independent predictor for reduced patient survival; miR-125b promoted NPC cell proliferation and inhibited NPC cell apoptosis; in a mouse model, administration of miR-125b antagomir significantly reduced the growth of NPC xenograft tumors. Mechanistically, we confirmed that A20 was a direct target of miR-125b, and found that activation of nuclear factor ?B (NF-?B) signaling pathway by A20 mediated miR-125b-promoting NPC cell proliferation and -inhibiting NPC cell apoptosis. With a combination of loss-of-function and gain-of-function approaches, we further showed that A20 inhibited NPC cell proliferation, induced NPC cell apoptosis, and reduced the growth of NPC xenograft tumors. Moreover, A20 was significantly downregulated, whereas p-p65(RelA) was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa, and miR-125b level was negatively associated with A20 level, whereas positively associated with p-p65 level. Our data demonstrate that miR-125b regulates NPC cell proliferation and apoptosis by targeting A20/NF-?B signaling pathway, and miR-125b acts as oncogene, whereas A20 functions as tumor suppressor in NPC, highlighting the therapeutic potential of miR-125b/A20/NF-?B signaling axis in the NPC.
Project description:<h4>Background</h4>To determine the correlation of cyclin-dependent kinase inhibitor 1B (p27) expression with clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient prognosis.<h4>Methods</h4>Real-time PCR and immunohistochemistry were used to examine the mRNA and protein expressions of p27 in NPC and nasopharyngeal tissues. The relationship of p27 expression levels with clinical features and prognosis of NPC patients was analyzed.<h4>Results</h4>The expression level of p27 mRNA was markedly lower in NPC tissues than that in the nasopharyngeal tissues (P?=?0.0006). Specific p27 protein staining by immunohistochemistry was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells but decreased expression was observed in NPC samples compared to normal epithelium samples (P?=?0.002). In addition, low levels of p27 protein were inversely correlated with the status of T classification (p?=?0.002) and clinical stage (p?=?0.019) of NPC patients. Patients with lower p27 expression had a significantly shorter overall survival time than did patients with high p27 expression. Multivariate analysis suggested that the level of p27 expression was not an independent prognostic indicator (p?=?0.682) for NPC survival.<h4>Conclusion</h4>Low level of p27 expression is a potential unfavorable prognostic factor for patients with NPC.<h4>Virtual slides</h4>The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1915282782109343.
Project description:MicroRNAs are biomarkers of prognosis and survival for many types of cancer. We evaluated whether microRNAs can predict the survival and efficacy of concurrent chemotherapy in nasopharyngeal carcinoma (NPC) patients. We retrospectively analyzed microRNA expression in 312 paraffin-embedded NPC specimens and 18 normal nasopharyngeal tissues using microarray. We found Forty-one microRNAs are differentially expressed between NPC and normal tissues, and a five-microRNA signature can predict survival independent of stage. NPC patients with the low-risk microRNA signature have a favorable response to concurrent chemotherapy. microRNA profiling of nasopharyngeal carcinoma tissues vs. normal nasopharyngeal tissues 312 paraffin-embedded nasopharyngeal carcinoma tissues and 18 paraffin-embedded normal nasopharyngeal tissues