eIF6 as a Promising Diagnostic and Prognostic Biomarker for Poorer Survival of Cutaneous Melanoma

Background: Skin cutaneous melanoma (SKCM) is the deadliest skin cancer and has the most rapidly increasing incidences among all cancer types. Previous research elucidated that melanoma can only be successfully treated with surgical abscission in the early stage. Therefore, reliable and specific biomarkers are crucial to melanoma diagnosis since it often looks like nevi in the clinical manifestations. Moreover, identifying key genes contributing to melanoma progression is also highly regarded as a potential strategy for melanoma therapy. In this respect, translation initiator eIF6 has been proved as a pro-tumor factor in several cancers. However, the role of eIF6 in the skin cutaneous melanoma progression and its potential as a prognostic marker is still unexplored. Methods: The immunochemical analysis of clinical specimens were served to assess eIF6 expression levels. Gene Expression Profiling Interactive Analysis (GEPIA) database consultations allowed us to find the survival rates of the eIF6-overexpressed patients. eIF6 cellular effects were evaluated in an eIF6-overexpressed A375 cell line constructed with a lentivirus. The analysis of down-stream effectors or pathways was conducted using C-Bioportal and STRING databases. Results: Our results revealed that eIF6 was highly over-expressed in melanomas compared to normal skin specimens, and thus the abnormally high level of eIF6 can be a diagnostic marker for melanoma. The in silica analysis indicated that patients with eIF6 over-expression had lower survival rates than that low-expression in SKCM. Meanwhile, similar results also could be found in the other four types of cancers. In vitro, over-expression of eIF6 increased the proliferation and migration of melanoma cells. Correspondingly, pan-cancer clustering analysis indicated the expression level of intermediate filament proteins was correlated with that of eIF6 expression. In our study, all over-expressed keratin proteins, in accordance with over-expressed eIF6, had a negative correlation with melanoma prognosis. Moreover, the decreased methylation level of keratin genes suggested a new potential regulation mode of eIF6. Conclusions: The up-regulated eIF6 could be a potential diagnostic and prognostic biomarker of melanoma. This study also provides insights into the potential role of eIF6 in pan-cancer epigenetic regulation

Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery

The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy

Human EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting as per cancer type neoplastic cells growth and immune infiltration

Objectives: The EVI2B (Ecotropic Viral Integration Site 2B) gene encodes a transmembrane glycoprotein pivotal in immunocytes maturation. Recent evidence implicated EV12B’s expression with human colon cancer progression. However, EVI2B’s downstream pathways affecting tumor growth and tumor-infiltrating cells remain unclear. Methods: We first studied the diagnostic and prognostic value of EVI2B in pan-cancers by utilizing a series of in silico tools and clinical samples. Then we identified the modulated transcriptional expression and DNA methylation in high EVI2B’s expression groups of the same three cancers. We verified via RT-PCR the effect of stable EVI2B knock-down on the expression of JAK/STAT-related genes in two immune cell lines and the acceleration of proliferation in four cancer cell lines. Finally, the regulation of leukocyte infiltration was studied using TIMER. Results: In SKCM and LUAD a heightened EVI2B’s expression promoted a better prognosis. Conversely, in LGG EVI2B’s upregulation concurred with a worse prognosis. EVI2B silencing enhanced the proliferation of the tumor cell lines. The hypermethylated genome strengthened EVI2B’s Janus-like effect in high EVI2B expressing SKCM and LUAD tumors. While the total DNA methylation was lower in high EVI2B expressing LGG. Further analysis revealed that multiple EVI2B-involved down-stream JAK-STAT genes also exhibited the Janus-like feature in SKCM, LUAD and LGG progression. Correspondingly, anti-tumor leukocytes infiltrated EVI2B high expressing SKCM and LUAD while more pro-tumor ones penetrated into EVI2B heightened LGG. Conclusions: EVI2B acts as a Janus-faced oncogene/antioncogene by differently affecting neoplastic cell proliferation rates and tumor-promoting or tumor-hindering immunocytes’ infiltration