Search

Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells. This phosphatase functions in a dual manner, pro-oncogenic or tumor-suppressive, depending on the type of cancer. To date, the tumor-suppressive role of DUSP6 has been demonstrated in pancreatic cancer, non-small cell lung cancer, esophageal squamous cell and nasopharyngeal carcinoma, and ovarian cancer. Its pro-oncogenic role has been observed in human glioblastoma, thyroid carcinoma, breast cancer, and acute myeloid carcinoma. Both roles of DUSP6 have been documented in malignant melanoma depending on the histological subtype of the cancer. Loss- or gain-of-function effects of DUSP6 in these cancers highlights the significance of this phosphatase in carcinogenesis. Development of methods that use the DUSP6 gene as a therapeutic target for cancer treatment or as a prognostic factor for diagnosis and evaluation of cancer treatment outcome has great potential. This review focuses on molecular characteristics of the DUSP6 gene and its role in cancers in the purview of development, progression, and cancer treatment outcome.

Background OTUB1 is a deubiquitin enzyme that plays important role in cancer-related events. Prompted by the lack of information about OTUB1's potential as a breast cancer molecular marker, this study is conducted to evaluate the significance of OTUB1 as a diagnostic tool based on its expression in MCF-7, as well as to validate its potential as a therapeutic target using network-based analysis. Methods Relative expression of OTUB1 in MCF-7 and MCF-10A was compared using bioinformatics analysis on microarray datasets obtained from Gene Expression Omnibus and validated by qPCR experiment. Protein-protein interaction (PPI) network was constructed using Cytoscape ver3.6.0 to analyse the topological position of OTUB1 in cancer and differentially expressed genes (DEGs) neighbourhoods. Results Microarray datasets analysis showed that OTUB1 expression value is significantly higher in MCF-7 in seven out of 16 probes with log(FC) value ranging from 0.24 to 1.43. This result is consistent with qPCR analysis, with qPCR showing a larger log(FC) value of 2.44–4.95. Despite a significant difference in some microarray probes and qPCR experiment, the fold change value is too small to ensure sensitivity in breast cancer diagnosis. Meanwhile, PPI network analysis revealed that OTUB1 is the immediate neighbour for 31 cancer proteins and DEGs ESR1 and BIRC3, a strategic topological position for perturbing cancer interactome. Conclusion Taken together, our findings suggest that OTUB1 is an unfavourable candidate for breast cancer diagnosis marker, but it could be a very promising molecular target for breast cancer therapeutic intervention.

Background A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. Methods The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Results Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. Conclusion NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication.