scholarly journals MiRNA Profiling in Plasma and Placenta of SARS-CoV-2-Infected Pregnant Women

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1788
Author(s):  
Irma Saulle ◽  
Micaela Garziano ◽  
Claudio Fenizia ◽  
Gioia Cappelletti ◽  
Francesca Parisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pregnant Women ◽  
Vertical Transmission ◽  
Mirna Expression ◽  
Therapeutic Target ◽  
Immune Reaction ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Potential Therapeutic Target ◽  
Qpcr Array

MicroRNAs are gene expression regulators associated with several human pathologies, including those generated by viral infections. Their role in SARS-CoV-2 infection and COVID-19 has been investigated and reviewed in many informative studies; however, a thorough miRNA outline in SARS-CoV-2-infected pregnant women (SIPW), at both systemic and placental levels, is missing. To fill this gap, blood and placenta biopsies collected at delivery from 15 asymptomatic SIPW were immediately analysed for: miRNA expression (n = 84) (QPCR array), antiviral/immune mRNA target expression (n = 74) (QGene) and cytokine/chemokines production (n = 27) (Multiplex ELISA). By comparing these results with those obtained from six uninfected pregnant women (UPW), we observed that, following SARS-CoV-2 infection, the transcriptomic profile of pregnant women is significantly altered in different anatomical districts, even in the absence of clinical symptoms and vertical transmission. This characteristic combination of miRNA and antiviral/immune factors seems to control both the infection and the dysfunctional immune reaction, thus representing a positive correlate of protection and a potential therapeutic target against SARS-CoV-2.

scholarly journals The SARS-CoV-2 conserved macrodomain is a mono-ADP-ribosylhydrolase

2020 ◽  
Author(s):  
Yousef M.O. Alhammad ◽  
Maithri M. Kashipathy ◽  
Anuradha Roy ◽  
Jean-Philippe Gagné ◽  
Peter McDonald ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Therapeutic Target ◽  
Viral Infections ◽  
Protein Domain ◽  
Structural Protein ◽  
Potential Therapeutic Target ◽  
Novel Therapeutic Strategies ◽  
Design And Testing ◽  
Translational Process ◽  
Novel Therapeutic

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like-CoVs encode 3 tandem macrodomains within non-structural protein 3 (nsp3). The first macrodomain, Mac1, is conserved throughout CoVs, and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. Mac1 likely counters host-mediated anti-viral ADP-ribosylation, a posttranslational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose. SARS-CoV-2, SARS-CoV and MERS-CoV Mac1 exhibit similar structural folds and all 3 proteins bound to ADP-ribose with low μM affinities. Importantly, using ADP-ribose detecting binding reagents in both a gel-based assay and novel ELISA assays, we demonstrated de-MARylating activity for all 3 CoV Mac1 proteins, with the SARS-CoV-2 Mac1 protein leading to a more rapid loss of substrate compared to the others. In addition, none of these enzymes could hydrolyze poly-ADP-ribose. We conclude that the SARS-CoV-2 and other CoV Mac1 proteins are MAR-hydrolases with similar functions, indicating that compounds targeting CoV Mac1 proteins may have broad anti-CoV activity.IMPORTANCESARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused greater than 900 thousand deaths worldwide. With, no currently approved treatments, novel therapeutic strategies are desperately needed. All coronaviruses encode for a highly conserved macrodomain (Mac1) that binds to and removes ADP-ribose adducts from proteins in a dynamic post-translational process increasingly recognized as an important factor that regulates viral infection. The macrodomain is essential for CoV pathogenesis and may be a novel therapeutic target. Thus, understanding its biochemistry and enzyme activity are critical first steps for these efforts. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose, and describe its ADP-ribose binding and hydrolysis activities in direct comparison to SARS-CoV and MERS-CoV Mac1 proteins. These results are an important first step for the design and testing of potential therapies targeting this unique protein domain.

scholarly journals The RNA helicase DDX5 promotes alveolar rhabdomyosarcoma growth and survival

2020 ◽  
Author(s):  
Alberto Gualtieri ◽  
Valerio Licursi ◽  
Chiara Mozzetta
Keyword(s):  
Gene Expression ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Therapeutic Target ◽  
Rna Helicase ◽  
Potential Therapeutic Target ◽  
Growth And Survival ◽  
Dead Box ◽  
Pharmacological Targets ◽  
Xenograft Models

AbstractRhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-ARMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Thus, other therapeutic vulnerabilities resulting from gene expression changes are progressively being recognized. Here, we identified the DEAD box RNA helicase 5 (DDX5) as a potential therapeutic target to inhibit FP-ARMS growth. We show that DDX5 is overexpressed in alveolar RMS cells, demonstrating that its depletion drastically decreases FP-ARMS viability and slows tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream the G9a/AKT survival signalling pathway, by modulating G9a protein stability. Finally, we show that G9a interacts with PAX3-FOXO1 and regulates its activity, thus sustaining FP-ARMS myoblastic state. Together, our findings identify a novel survival-promoting loop in FP-ARMS and highlight DDX5 as potential therapeutic target to arrest rhabdomyosarcoma growth.

scholarly journals Circular RNA circFAT1(e2) Promotes Osteosarcoma Progression and Metastasis by Sponging miR-181b and Regulating HK2 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Jun Xu ◽  
Kaifeng Zhou ◽  
Chong Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Therapeutic Target ◽  
Critical Role ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Expression Level ◽  
Circular Rnas ◽  
Competing Endogenous Rna ◽  
Potential Therapeutic Target

As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.

scholarly journals Depletion of procathepsin D gene expression by RNA interference – A potential therapeutic target for breast cancer

2007 ◽  
Vol 6 (7) ◽  
pp. 1081-1087 ◽  
Author(s):  
Sujata S. Ohri ◽  
Aruna Vashishta ◽  
Mary Proctor ◽  
Martin Fusek ◽  
Vaclav Vetvicka
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Rna Interference ◽  
Therapeutic Target ◽  
Potential Therapeutic Target

scholarly journals Characteristics, clinical and laboratory data and outcomes of pregnant women with confirmed SARS-CoV-2 infection admitted to Al-Zahra tertiary referral maternity center in Iran: a case series of 24 patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Vaezi ◽  
Mojgan Mirghafourvand ◽  
Shahla Hemmatzadeh
Keyword(s):  
Pregnant Women ◽  
Vertical Transmission ◽  
Clinical Symptoms ◽  
Laboratory Data ◽  
Case Series ◽  
Neonatal Morbidity ◽  
Maternity Hospital ◽  
Premature Labor ◽  
Normal Ranges ◽  
Clinical Records

Abstract Background Physiological changes during pregnancy put pregnant women at higher risk for COVID-19 complications. The objective of this study was to evaluate clinical and laboratory characteristics and outcomes of 24 COVID-19 pregnant patients and their newborns referred to the Al-Zahra tertiary maternity hospital in Tabriz, Iran. Methods Clinical records of 24 COVID-19 confirmed pregnant patients were retrospectively reviewed from10 March 2020 to 15 April 2020. Vertical transition was assessed through neonatal pharyngeal swab samples. The study has been approved by the Tabriz University Medical Ethics Committee (IR.TBZMED.REC.1399.497). Results There were 24 hospitalized cases with clinical symptoms and confirmed diagnosis of COVID-19. The mean age of cases was 26.5 years; most were nulliparous (54.2%), in their third trimester (62.5%) and were in the type A blood group. Clinical symptoms in order of prevalence were cough, fever, dyspnea, myalgia, anosmia, and diarrhea. Oxygen saturation (SpO2) in 70.8% cases was in the normal range (greater than 93%). The risk of premature labor or abortion in cases showed no increase. 12 cases were in ongoing normal status; on follow up, 11 cases had delivered their babies at term and one had ended in IUFD because of pregnancy-induced hypertension. All delivered babies were healthy. Caesarean section in all cases was performed under obstetric indications or maternal demand, and no relation was found between COVID-19 and Caesarean delivery. Neonatal outcomes according to gestational age in 8 cases out of 11 (72.72%) were desirable; neonatal morbidity and mortality resulted from pregnancy complications. Blood pH in 6 neonates was assessed due to immaturity and NICU admission, all of which were in normal ranges except one case related to HELLP syndrome. There was no evidence of vertical transmission. Conclusions Findings suggest that clinical symptoms in pregnancy were similar to non-pregnant women, no rise in risk of premature labor or abortion was seen, and vertical transmission was not observed in none of cases. Lymphopenia was the leading laboratory change. Given asymptomatic cases despite severe forms of infection in pregnancies, we propose screening in all suspected cases. All placentas and newborns should be tested in the field for vertical transmission.

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