Identification and analysis of oncogenic non-synonymous single nucleotide polymorphisms in the human NRAS gene: An exclusive in silico study.

BACKGROUND: N-ras protein is encoded by the NRAS gene and operates as GDP-GTP-controlled on/off switching. N-ras interacts with cellular signaling networks that regulate various cellular activities including cell proliferation and survival. The nonsynonymous single nucleotide polymorphism (nsSNPs)-mediated alteration can substantially disrupt the structure and activity of the corresponding protein. N-ras has been reported to be associated with numerous diseases including cancers due to the nsSNPs. A comprehensive study on the NRAS gene to unveil the potentially damaging and oncogenic nsSNPs is yet to be accomplished. Hence, this extensive in silico study is intended to identify the disease-associated, specifically oncogenic nsSNPs of the NRAS gene. RESULTS: Out of 140 missense variants, 7 nsSNPs (I55R, G60E, G60R, Y64D, L79F, D119G, and V152F) were identified to be damaging utilizing 10 computational tools that works based on different algorithms with high accuracy. Among those, G60E, G60R, and D119G variants were further filtered considering their location in the highly conserved region and later identified as oncogenic variants. Interestingly, G60E and G60R variants were revealed to be particularly associated with lung adenocarcinoma, rhabdomyosarcoma, and prostate adenocarcinoma. Therefore, D119G could be subjected to detailed investigation for identifying its association with specific cancer. CONCLUSION: This in silico study identified the deleterious and oncogenic missense variants of the human NRAS gene that could be utilized for designing further experimental investigation. The outcomes of this study would be worthwhile in future research for developing personalized medicine.

A Computational Approach to Justifying Stratifin as a Candidate Diagnostic and Prognostic Biomarker for Pancreatic Cancer.

Pancreatic cancer (PC) is considered a silent killer because it does not show specific symptoms at an early stage. Thus, identifying suitable biomarkers is important to avoid the burden of PC. Stratifin (SFN) encodes the 14-3-3σ protein, which is expressed in a tissue-dependent manner and plays a vital role in cell cycle regulation. Thus, SFN could be a promising therapeutic target for several types of cancer. This study was aimed at investigating, using online bioinformatics tools, whether SFN could be used as a diagnostic and prognostic biomarker in PC. SFN expression was explored by utilizing the ONCOMINE, UALCAN, GEPIA2, and GENT2 tools, which revealed that SFN expression is higher in PC than in normal tissues. The clinicopathological analysis using the ULCAN tool showed that the intensity of SFN expression is commensurate with cancer progression. GEPIA2, R2, and OncoLnc revealed a negative correlation between SFN expression and survival probability in PC patients. The ONCOMINE, UCSC Xena, and GEPIA2 tools showed that cofilin 1 is strongly coexpressed with SFN. Moreover, enrichment and network analyses of SFN were performed using the Enrichr and NetworkAnalyst platforms, respectively. Receiver operating characteristic (ROC) curves revealed that tissue-dependent expression of the SFN gene could serve as a diagnostic and prognostic biomarker. However, further wet laboratory studies are necessary to determine the relevance of SFN expression as a biomarker.

Antioxidant, cytotoxic and antineoplastic effects of Carissa carandas Linn. leaves.

For scientific clarification of some traditional uses, this study was designed to explore the antioxidant, cytotoxic and antineoplastic properties of leaf extract of Carissa carandas Linn., a traditional medicinal plant of Bangladesh. The methanol extract of Carissa carandas leaves (MELC) was applied on DPPH and ABTS experiments to determine its antioxidant activity. In vitro the cytotoxic effect of MELC was evaluated against colonic adenocarcinoma cell lines (SW-480 and SW-48) whereas in vivo its antineoplastic property was tested against Ehrlich ascites carcinoma (EAC). The DPPH and ABTS assays revealed the antioxidant activity of MELC with IC50 10.5±1.2 and 1.75±0.3µg/ml that was comparable to L-ascorbic acid. In vitro cytotoxic study, MELC reduced the viability of adenocarcinoma cells in dose dependent manner and in vivo, administration of MELC (25mg/kg) resulted in a significant (p<0.05) decrease in viable EAC cell count thereby increasing the life span of the EAC cell bearing mice. Restoration of hematological parameters such as red blood cells (RBC), hemoglobin and white blood cells (WBC) to normal levels in MELC-treated mice was also observed. Moreover, treatment with MELC induced apoptosis of EAC cells as observed in fluorescence microscopic view of DAPI (4,6-diamidino-2-phenylindole) stained cells and also increased p53 gene expression MELC-treated cells in respect to untreated EAC control. In addition, the MELC was rich in polyphenol content and its GC-MS chromatogram confirmed the presence of some compounds all of which showed anticancer and cytotoxic activities in previous studies. In a word, this study supports the use of Carissa carandas in traditional medicine as well as highlights the need to further explore the potentials of MELC as an antineoplastic agent.