The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein.

BACKGROUND: The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. METHODS: Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc. RESULTS: Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. CONCLUSION: Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy.

Suppression of oncogenic protein translation via targeting eukaryotic translation initiation factor 4E overcomes chemo-resistance in nasopharyngeal carcinoma.

Resistance to adjuvant chemotherapy remains therapeutic challenge in nasopharyngeal carcinoma (NPC). In this work, we demonstrate that targeting eukaryotic translation initiation factor 4E (eIF4E) is a potential sensitizing strategy to overcome chemoresistance in NPC. We observe the aberrant activation of eIF4E and translational upregulation of eIF4E-regulated oncogenes in NPC cell after pro-longed exposure of cisplatin. Functional analysis demonstrates that eIF4E depletion effectively inhibits proliferation and induces apoptosis in cisplatin-resistant NPC cells. Consistently, eIF4E knockdown significantly enhances cisplatin efficacy in cisplatin-sensitive cells. We identify eIF4E as a therapeutically actionable targets by showing that ribavirin, an anti-viral drug, phenocopies the effects of eIF4E knockdown in NPC. We further demonstrate that ribavirin acts on chemoresistant NPC cells through suppressing eIF4E activity and oncogenic protein translation. Using two independent NPC xenograft mouse models, we show that ribavirin not only is effective in inhibiting chemoresistant NPC growth but also significantly augments the inhibitory effects of cisplatin efficacy in vivo without causing significant toxicity in mice. Taken together, our work shows an activation of eIF4E-mediated growth and survival mechanisms in response to chemotherapy and suggests that inhibition of eIF4E activity represents an attractive sensitizing strategy for NPC treatment. Our findings also suggest that ribavirin is a useful addition to the treatment armamentarium for NPC.

Association between routine hematological parameters and sudden sensorineural hearing loss: A meta-analysis.

OBJECTIVE: Recent studies have shown that chronic inflammation contributes to the development of sudden sensorineural hearing loss (SSNHL). Some hematologic parameters have also been linked to the prognosis of SSNHL. However, the prognostic value of such hematological factors is not conclusive. This study explored the association of routine hematological parameters with SSNHL. METHODS: A systematic literature search was conducted in PubMed, Cochrane Library, Web of Science and Embase to identify eligible studies. Standardized mean deviation (SMD) and the 95% confidence interval (CI) were retried from relevant studies for analysis. Heterogeneity, subgroup, and publication bias analyses were performed. RESULTS: A total of 18 studies involving 1505 SSNHL patients and 1466 healthy persons were enrolled in the final analysis. The study population included 699 responders and 458 non-responders to treatment. Pooled results revealed that the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) value in the SSNHL patient group were higher than in the healthy group (SMD = 1.05, 95% CI: 0.86,1.24, p < 0.001, SMD = 0.52, 95% CI: 0.26,0.78, p < 0.001, respectively). However, there was no significant difference in the mean platelet volumes (MPV) between the groups (SMD = 0.03, 95% CI: 0.44, 0.49, p = 0.91). Notably, NLR and PLR values were evidently higher in the unrecovered group than in the recovered group (SMD = -0.63, 95% CI: 1.02, -0.23, p = 0.002, SMD = -0.4, 95% CI: 0.76, -0.03, p = 0.03, respectively). However, the MPV value was similar in both groups (SMD = -0.35, 95% CI: 1.14,0.44, p = 0.38). CONCLUSIONS: Our results show that NLR and PLR values can predict the onset and prognosis of SSNHL.

Highly expressed CCR7 predicts poor prognosis in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NC) is a malignant human tumor with a high incidence that occurs on the top and lateral wall of the nasopharynx. AIMS: To investigate the clinical value of chemokine receptor 7 (CCR7) in locally advanced NC. METHODS: We enrolled 114 patients with locally advanced NC admitted to our hospital in the observation group (OBG) and 100 normal healthy subjects who underwent physical examination in the control group (COG). The serum CCR7 expression levels in each group were measured using enzyme-linked immunosorbent assay and were compared between the groups. RESULTS: None of the 114 patients or their family members were lost during follow-up. Thirty-five patients died within 3 years and 79 survived (survival rate: 69.29%). The serum CCR7 level was higher in the OBG than in the COG (P < 0.05). The receiver operating characteristic (ROC) curve showed that the area under the ROC curve (AUC) was 0.837 for diagnostic value for locally advanced NC and the AUC was 0.759 for predictive value for 3-year mortality. The CCR7 AUC for diagnosis of locally advanced NC was 0.837 and for prediction of mortality was 0.759. Univariate analysis revealed significant differences in smoking history, long-term consumption of pickled food, family history of NC, primary lesion staging, lymph node staging, distant metastasis, clinical pathological staging, and CCR7 between the two groups (P < 0.05). CONCLUSIONS: CCR7 was valuable in the diagnosis of locally advanced NC, and highly expressed CCR7 was predictive of poor prognosis.

[A case report of isolated marginal zone B cell lymphoma originating from the parapharyngeal space].

This is a case report of isolated marginal zone B cell lymphoma originating from the parapharyngeal space and reaching up to the side of skull base. There are no obvious clinical symptoms of the marginal zone B cell lymphoma originating in the parapharyngeal space, the imaging examination of which showed slightly blurred edge mass shadow with heterogeneous textures and no specificity. The pathological examination revealed a large number of lymphocyte proliferation, which was not specific yet. Immunohistochemistry may show the tumor was monoclonal and positive to CD20 and CD79a positive. Marginal zone B cell lymphoma originating in the parapharyngeal space is a rare tumor with no specific clinical symptoms or early signs, and is easily misdiagnosed. The diagnosis should be confirmed based on pathological and immunohistochemical examination, and the tumor can be treated by surgery combined with chemotherapy.