In silico Analysis of Molecular Mechanisms of Galanthus nivalis Agglutinin-Related Lectin-Induced Cancer Cell Death from Carbohydrate-Binding Motif Evolution Hypothesis

MicroRNA-122 (miR-122) is liver specific and plays an important role in physiology as well as diseases including hepatocellular carcinoma (HCC). Downregulation of miR-122 in HCC modulates apoptosis. Similarly, the putative targets of miR-122, the forkhead box (FOX) family genes also play an important role in the regulation of apoptosis. Hence, an interplay between miR-122 and FOX family genes has been explored in this study. Initially, an augmentation of apoptosis was noticed in HepG2 cells after transfection with miR-122. Further, the predicted miR-122 targets, the FOX family genes ( FOXM1b, FOXP1, and FOXO4) were selected via in silico analysis based on their role in apoptosis. We checked the expression of all these genes at transcript level after the transfection of miR-122 and found that the relative expression of FOXP1 and FOXM1b was significantly downregulated (p < 0.005) and that of FOXO4 was upregulated (p < 0.005). Thus, the finding indicates deregulation of these FOX genes as a result of miR-122 augmentation might be involved in the modulation of apoptosis. Impact Statement Here, we have investigated the crosstalk between microRNA-122 (miR-122) and selective FOX family genes in HepG2 cells. miR-122 is a prominent miRNA in liver and has been reported to be downregulated in hepatocellular carcinoma (HCC). It has been speculated that diminished level of miR-122 during HCC might be one of the reasons for tumor progression. However, the exact molecular interactions are not clear yet. This study unravels one of the molecular mechanisms of miR-122 through which it might impact the tumorigenesis of HCC.

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In silico analysis of carbohydrate-binding pockets in the lectin genes from various species of Canavalia

Computational Biology and Chemistry ◽

10.1016/j.compbiolchem.2021.107477 ◽

2021 ◽

pp. 107477

Author(s):

Ramanathan Nivetha ◽

Mani Meenakumari ◽

Sreeramulu Bhuvaragavan ◽

Karuppiah Hilda ◽

Sundaram Janarthanan

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Carbohydrate Binding ◽

Binding Pockets ◽

Lectin Genes ◽

Silico Analysis

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Editorial [Hot topic: Molecular Mechanisms of Cancer Cell Death (Executive Editor: Ricardo Perez-Tomas)]

Current Pharmaceutical Design ◽

10.2174/138161210789941829 ◽

2010 ◽

Vol 16 (1) ◽

pp. 1-2

Author(s):

Ricardo Perez-Tomas

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Molecular Mechanisms ◽

Executive Editor ◽

Cancer Cell Death

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Molecular mechanisms of prostate cancer cell death upon inhibition of arachidonate 5-lipoxygenase: Involvement of FAS/APO1-mediated signals

Prostaglandins & Other Lipid Mediators ◽

10.1016/s0090-6980(99)90318-0 ◽

1999 ◽

Vol 59 (1-6) ◽

pp. 83

Author(s):

Jagadananda Ghosh ◽

Charles E. Myers

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Cancer Cell ◽

Molecular Mechanisms ◽

Prostate Cancer Cell ◽

Cancer Cell Death

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An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates

10.1101/2021.12.18.21267908 ◽

2021 ◽

Author(s):

Ashutosh Kumar ◽

Adil Asghar ◽

Himanshu N. Singh ◽

Muneeb A. Faiq ◽

Sujeet Kumar ◽

...

Keyword(s):

In Silico ◽

Immune Escape ◽

Mutational Analysis ◽

In Silico Analysis ◽

Spike Protein ◽

World Health ◽

Genomic Sequences ◽

Binding Motif ◽

New Variant ◽

Silico Analysis

Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

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Genome-Wide Discovery of miRNAs with Differential Expression Patterns in Responses to Salinity in the Two Contrasting Wheat Cultivars

International Journal of Molecular Sciences ◽

10.3390/ijms222212556 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12556

Author(s):

Muhammad Zeeshan ◽

Cheng-Wei Qiu ◽

Shama Naz ◽

Fangbin Cao ◽

Feibo Wu

Keyword(s):

Salt Tolerance ◽

Salinity Stress ◽

In Silico ◽

Molecular Mechanisms ◽

In Silico Analysis ◽

Wheat Cultivars ◽

Target Mrnas ◽

Putative Target ◽

Genome Wide ◽

Silico Analysis

Salinity is a serious environmental issue. It has a substantial effect on crop yield, as many crop species are sensitive to salinity due to climate change, and it impact is continuing to increase. Plant microRNAs (miRNAs) contribute to salinity stress response in bread wheat. However, the underlying molecular mechanisms by which miRNAs confer salt tolerance in wheat are unclear. We conducted a genome-wide discovery study using Illumina high throughput sequencing and comprehensive in silico analysis to obtain insight into the underlying mechanisms by which small RNAs confer tolerance to salinity in roots of two contrasting wheat cvv., namely Suntop (salt-tolerant) and Sunmate (salt-sensitive). A total of 191 microRNAs were identified in both cultivars, consisting of 110 known miRNAs and 81 novel miRNAs; 181 miRNAs were shared between the two cultivars. The known miRNAs belonged to 35 families consisted of 23 conserved and 12 unique families. Salinity stress induced 43 and 75 miRNAs in Suntop and Sunmate, respectively. Among them, 14 and 29 known and novel miRNAs were expressed in Suntop and 37 and 38 in Sunmate. In silico analysis revealed 861 putative target mRNAs for the 75 known miRNAs and 52 putative target mRNAs for the 15 candidate novel miRNAs. Furthermore, seven miRNAs including tae-miR156, tae-miR160, tae-miR171a-b, tae-miR319, tae-miR159a-b, tae-miR9657 and novel-mir59 that regulate auxin responsive-factor, SPL, SCL6, PCF5, R2R3 MYB, and CBL-CIPK, respectively, were predicted to contribute to salt tolerance in Suntop. This information helps further our understanding of how the molecular mechanisms of salt tolerance are mediated by miRNAs and may facilitate the genetic improvement of wheat cultivars.

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