scholarly journals Plant Microrna Potential in Targeting COVID-19 Genome Offering Efficient Antiviral Mirna-based Therapies

2021 ◽  
Author(s):  
Behzad Hajieghrari ◽  
Sara Rahmanian-Koshkaki
Keyword(s):  
Mirna Target ◽  
Protein Translation ◽  
Plant Mirnas ◽  
Novel Therapy ◽  
Great Chance ◽  
Virus Rna ◽  
Cell Gene Expression ◽  
Target Binding

Abstract In 2019, the seventh member of the Coronaviridae named severe acute respiratory coronavirus II (or COVID-19) emerged in Wuhan, China. It could rapidly turn into a global pandemic. Therefore, searching for a natural/ novel therapy is urgently essential to prevent disease distribution. Based on the principle of cross-kingdom interaction, plants are a candidate as a potential source of exogenous miRNAs that can efficiently affect the host cell gene expression by promote target mRNA degradation or repress protein translation, and, or virus RNA translation/replication. The possibility of taking up the diet-derived plant-originated/artificially miRNA(s) in addition to their biological role in the host provides a pivotal clue for the study of synthesized/artificially expressed active therapeutic plant-originated miRNA(s) to promote antiviral activity. In this study, plant miRNAs, which can potentially interact with the COVID-19 genome within the 3’-UTR region and prompt antiviral function, were searched using bioinformatics approaches. RNAHybrid, RNA22, and STarMir miRNA/target detection tools were served for the possible plant miRNA/target recognition on the 3’-UTR flanking region of the COVID-19 genome by different algorithms. The RNAHybrid algorithm resulted in 63 plant miRNAs having hybridization energy with less or equal to -25 kcal/mol. They interact with diverse classes of miRNA/target binding patterns. However, each RNA22 and STarMir tools identified eight probable miRNA/target interaction candidates, in which pvu-miR159a.2 and sbi-miR5387b detected by both the RNA22 and STarMir tools at the same position. For us, they are suitable plant-derived miRNA candidates, which have the great chance of targeting the COVID-19 genome in the 3’-UTR region in vitro to induce the virus degradation and translational repression and for antiviral miRNA-based therapies without any side effects in vivo.

scholarly journals Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Manuel Pedro Jimenez-García ◽  
Antonio Lucena-Cacace ◽  
Daniel Otero-Albiol ◽  
Amancio Carnero
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Neural Crest ◽  
Tumor Suppressors ◽  
Homeobox Genes ◽  
Neuronal Cell ◽  
Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

scholarly journals EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling

2021 ◽  
Author(s):  
Liqing Jia ◽  
Xiaolu Ge ◽  
Chao Du ◽  
Linna Chen ◽  
Yanhong Zhou ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Protein Interactions ◽  
Elongation Factor ◽  
Protein Translation ◽  
Protein Protein Interactions ◽  
Promising Target ◽  
Tgfβ Receptor ◽  
Mesenchymal Transformation

Abstract Background Eukaryotic protein translation elongation factor 1α2 (EEF1A2) is an oncogene that promotes the progression of breast and pancreatic cancer. In this study, we aimed to elucidate the oncogenic function of EEF1A2 in the metastasis of lung adenocarcinoma (LUAD). Methods Immunohistochemistry and western blot were used to study EEF1A2 expression levels in LUAD tissues and cells, respectively. The role of EEF1A2 in LUAD progression were investigated in vitro and in vivo. We identified potential EEF1A2-binding proteins by liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. Protein–protein interactions were determined by immunofluorescence and co-immunoprecipitation (Co-IP). Results In this study, we report that EEF1A2 mediates the epithelial–mesenchymal transformation (EMT), to promote the metastasis of LUAD cells in vitro and in vivo. Moreover, EEF1A2 interacts with HSP90AB1 to increase TGFβ Receptor (TβR)-I, and TβRII expression, followed by enhanced SMAD3 and pSMAD3 expression and nuclear localisation, which promotes the EMT of LUAD cells. Overexpression of EEF1A2 in cancer tissues is associated with poor prognosis and short survival of patients with LUAD. Conclusions These findings underscore the molecular functions of EEF1A2 in LUAD metastasis and indicate that EEF1A2 represents a promising target in the treatment of aggressive LUAD.

scholarly journals In Vitro Import of a Nuclearly Encoded tRNA into Mitochondria of Solanum tuberosum

2003 ◽  
Vol 23 (11) ◽  
pp. 4000-4012 ◽  
Author(s):  
Ludovic Delage ◽  
André Dietrich ◽  
Anne Cosset ◽  
Laurence Maréchal-Drouard
Keyword(s):  
Solanum Tuberosum ◽  
Higher Plants ◽  
Plant Mitochondria ◽  
Protein Translation ◽  
Trna Genes ◽  
Vitro Assay ◽  
Trna Import

ABSTRACT Some of the mitochondrial tRNAs of higher plants are nuclearly encoded and imported into mitochondria. The import of tRNAs encoded in the nucleus has been shown to be essential for proper protein translation within mitochondria of a variety of organisms. Here, we report the development of an in vitro assay for import of nuclearly encoded tRNAs into plant mitochondria. This in vitro system utilizes isolated mitochondria from Solanum tuberosum and synthetic tRNAs transcribed from cloned nuclear tRNA genes. Although incubation of radioactively labeled in vitro-transcribed tRNAAla, tRNAPhe, and tRNAMet-e with isolated potato mitochondria resulted in importation, as measured by nuclease protection, the amount of tRNA transcripts protected at saturation was at least five times higher for tRNAAla than for the two other tRNAs. This difference in in vitro saturation levels of import is consistent with the in vivo localization of these tRNAs, since cytosolic tRNAAla is naturally imported into potato mitochondria whereas tRNAPhe and tRNAMet-e are not. Characterization of in vitro tRNA import requirements indicates that mitochondrial tRNA import proceeds in the absence of any added cytosolic protein fraction, involves at least one protein component on the surface of mitochondria, and requires ATP-dependent step(s) and a membrane potential.

scholarly journals Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing

2010 ◽  
Vol 19 (4) ◽  
pp. 399-408 ◽  
Author(s):  
Sina Y. Rabbany ◽  
Joseph Pastore ◽  
Masaya Yamamoto ◽  
Tim Miller ◽  
Shahin Rafii ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stromal Cell ◽  
Wound Closure ◽  
Tissue Injury ◽  
Unmet Need ◽  
Novel Therapy ◽  
Yorkshire Pigs ◽  
Stromal Cell Derived Factor

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

scholarly journals Olaparib and Enzalutamide synergistically suppress HCC progression via the AR-mediated miR-146a-5p/BRCA1 signaling

2019 ◽  
Author(s):  
Jie Zhao ◽  
Yin Sun ◽  
Hui Lin ◽  
Fuju Chou ◽  
Yao Xiao ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Parp Inhibitor ◽  
Preclinical Study ◽  
Brca1 Expression ◽  
Novel Therapy ◽  
Damage Response ◽  
Synergistic Mechanism ◽  
Direct Binding

AbstractHepatocellular carcinoma (HCC) is one of most common malignant tumors worldwide, however, the treatment for advanced HCC remains unsatisfactory. Here we found that Olaparib, a FDA approved PARP inhibitor, could enhance the cytotoxicity in HCC cells with a lower BRCA1 expression, and suppressing the AR with either Enz or AR-shRNA could further increase the Olaparib sensitivity to better suppress the HCC cell growth via a synergistic mechanism that may involve suppressing the expression of BRCA1 and other DNA damage response (DDR) genes. Mechanism studies revealed that Enz/AR signaling might transcriptional regulting the miR-146a-5p expression via binding to the AREs on its 5’ promoter region, which could then lead to suppress the homologous recombination-related BRCA1 expression via direct binding to its 3’ UTR of mRNA. Preclinical study using an in vivo mouse model also proved that combined Enz plus Olaparib led to better suppression of the HCC progression. Together, these in vitro/in vivo data suggest that combining Enz and Olaparib may help in the development of a novel therapy to better suppress the HCC progression.

scholarly journals Preeclampsia: Сardiotonic Steroids, Fibrosis and a Hint to Cancerogenesis

2020 ◽  
Author(s):  
Alexei Bagrov ◽  
Nikolai Kolodkin ◽  
C. David Adair ◽  
Natalia Agalakova ◽  
Alexandr Trashkov
Keyword(s):  
Inverse Relationship ◽  
Therapeutic Strategy ◽  
Transcriptional Factor ◽  
Negative Regulator ◽  
Novel Therapy ◽  
Mortality And Morbidity ◽  
Maternal Mortality And Morbidity ◽  
Leading Position

Despite prophylaxis and attempts to select a therapy, the frequency of preeclampsia does not decrease, and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present a new theory of the etiology and pathogenesis of preeclampsia which is based on the interaction of Na/K-ATPase and its endogenous ligands including marinobufagenin. The signaling pathway of marinobufagenin involves an inhibition of transcriptional factor Fli1, a negative regulator of collagen synthesis, followed by deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer: since Fli1 is a proto-oncogene, a hypothesis on suppression of Fli1 by cardiotonic steroids as potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia which is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable to impair marinobufagenin-Na/K-ATPase interactions.

scholarly journals Remodeling tumor microenvironment by liposomal co-delivery of DMXAA and simvastatin inhibits malignant melanoma progression

2021 ◽  
Author(s):  
Valentin Florian Rauca ◽  
Laura Patras ◽  
Lavinia Luput ◽  
Emilia Licarete ◽  
Vlad Alexandru Toma ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Novel Therapy ◽  
Drug Induced ◽  
Angiogenic Therapy ◽  
Melanoma Model ◽  
M1 Phenotype

Anti-angiogenic therapies for melanoma have not yet been translated into meaningful clinical benefit for patients, due to development of drug-induced resistance in cancer cells, mainly caused by hypoxia-inducible factor 1α (HIF-1α) overexpression and enhanced oxidative stress mediated by tumor-associated macrophages (TAMs). Our previous study demonstrated synergistic antitumor actions of simvastatin (SIM) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on an in vitro melanoma model via suppression of the aggressive phenotype of melanoma cells and inhibition of TAMs-mediated angiogenesis. Therefore, we took the advantage of long circulating liposomes (LCL) superior tumor targeting capacity to efficiently deliver SIM and DMXAA to B16.F10 melanoma in vivo, with the final aim of improving the outcome of the anti-angiogenic therapy. Thus, we assessed the effects of this novel combined tumor-targeted treatment on s.c. B16.F10 murine melanoma growth and on the production of critical markers involved in tumor development and progression. Our results showed that the combined liposomal therapy inhibited almost totally the growth of melanoma tumors, due to the enhancement of anti-angiogenic effects of LCL-DMXAA by LCL-SIM and induction of a pro-apoptotic state in the tumor microenvironment (TME). These effects were favoured by the partial re-education of TAMs towards a M1 phenotype and maintained via suppression of major invasion and metastasis promoters (HIF-1α, pAP-1 c-Jun, and MMPs). Thus, this novel therapy holds the potential to remodel the tumor microenvironment, by suppressing its most important malignant biological capabilities.

scholarly journals Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

scholarly journals The efficacy and safety of cold atmospheric plasma as a novel therapy for diabetic wound in vitro and in vivo

2020 ◽  
Vol 17 (3) ◽  
pp. 851-863 ◽  
Author(s):  
Rui He ◽  
Qin Li ◽  
Wenqi Shen ◽  
Tao Wang ◽  
Huijuan Lu ◽  
...  
Keyword(s):  
Atmospheric Plasma ◽  
Diabetic Wound ◽  
Efficacy And Safety ◽  
Novel Therapy ◽  
Cold Atmospheric Plasma

scholarly journals Suppression of MicroRNA 200 Family Expression by Oncogenic KRAS Activation Promotes Cell Survival and Epithelial-Mesenchymal Transition in KRAS-Driven Cancer

2016 ◽  
Vol 36 (21) ◽  
pp. 2742-2754 ◽  
Author(s):  
Xiaomin Zhong ◽  
Lan Zheng ◽  
Jianfeng Shen ◽  
Dongmei Zhang ◽  
Minmin Xiong ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Protein Translation ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Regulate Gene Expression ◽  
Mesenchymal Transition ◽  
Pancreatic Cancers ◽  
Mcf10a Cells

Oncogenic KRAS contributes to malignant transformation, antiapoptosis, and metastasis in multiple human cancers, such as lung, colon, and pancreatic cancers and melanoma. MicroRNAs (miRNAs) are endogenous 18- to 25-nucleotide noncoding small RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or inhibition of protein translation. In the present study, using array-based miRNA profiling in IMR90 and MCF10A cells expressing oncogenic KRAS, we identified that the expression of the microRNA 200 (mir-200) family was suppressed by KRAS activation and that this suppression was mediated by the transcription factors JUN and SP1 in addition to ZEB1. Restoration of mir-200 expression compromised KRAS-induced cellular transformationin vitroand tumor formationin vivo. In addition, we found that enforced expression of mir-200 abrogated KRAS-induced resistance to apoptosis by directly targeting the antiapoptotic geneBCL2. Finally, mir-200 was able to antagonize the epithelial-mesenchymal transition (EMT) driven by mutant KRAS. Collectively, our results suggest that repression of endogenous mir-200 expression is one of the important cellular responses to KRAS activation during tumor initiation and progression.

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