Expression and Functional Assessment of Some Featured Coding and Non-coding RNAs Encoded by 8q24 Chromosomal Region in CML Patients

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mina Zamani ◽  
Hamid Galehdari ◽  
Babak Bakhshinejad ◽  
Mohammad-Reza Hajjari ◽  
Ali-Mohammad Foroughmand

Background: The association between the human chromosomal 8q24 region and cancer development remains dim. The proto-oncogene MYC is known as the most prominent target of this chromosomal region. However, numerous cancer-associated genetic alterations in the region extend beyond the MYC locus. Accordingly, it is likely that the MYC oncogene is not the only target of these carcinogenesis-related alterations. Objectives: In the present study, the expression of MYC and the correlation between MYC and two non-coding RNAs, namely PVT1 (circular and linear forms) and CASC11, which are residents of the 8q24 region in the MYC neighborhood, were investigated in chronic myeloid leukemia (CML). Methods: Real-time polymerase chain reaction (PCR) was used to assess BCR-ABL transcripts and categorize positive and negative (normal) samples for CML. Afterward, real-time PCR was exploited to evaluate the expression of different genes, including MYC, linear PVT1, circular PVT (CircPVT1), CASC11, and ACTB in CML and normal samples. Results: We found that the expression of linear PVT1 is significantly increased in CML compared with normal samples. However, CircPVT1, CASC11, and MYC did not show significantly altered expression between CML and normal groups. The experimental and in silico analyses of the correlation coefficients of gene expressions suggested changes in the correlations between the gene expressions in CML compared with normal samples. We also assessed the miR-trapping potential of PVT1 and CASC11 and the possible effects of these interactions on signaling pathways. Our findings indicated that these lncRNAs could have a possible regulatory link with critical pathways associated with leukemogenesis. Conclusions: Our results indicate that non-coding genes surrounding MYC within the 8q24 region might have regulatory roles in CML carcinogenesis.

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqun Zhang ◽  
Fengju Chen ◽  
Lawrence A. Donehower ◽  
Michael E. Scheurer ◽  
Chad J. Creighton

AbstractThe global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children’s Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.


Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 527 ◽  
Author(s):  
Sonali Pal ◽  
Manoj Garg ◽  
Amit Kumar Pandey

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanaz Dehbashi ◽  
Hamed Tahmasebi ◽  
Behrouz Zeyni ◽  
Mohammad Reza Arabestani

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA)-bloodstream infections (BSI) are predominantly seen in the hospital or healthcare-associated host. Nevertheless, the interactions of virulence factor (VFs) regulators and β-lactam resistance in MRSA-BSI are unclear. This study aims to characterize the molecular relationship of two-component systems of VFs and the expression of the β-lactamase gene in MRSA-BSI isolates. In this study, 639 samples were collected from BSI and identified by phenotypic methods. We performed extensive molecular characterization, including SCCmec type, agr type, VFs gene profiles determinations, and MLST on isolates. Also, a quantitative real-time PCR (q-RT PCR) assay was developed for identifying the gene expressions. Results Ninety-one (91) S. aureus and 61 MRSA (67.0%) strains were detected in BSI samples. The presence of VFs and SCCmec genes in MRSA isolates were as follows: tst (31.4%), etA (18.0%), etB (8.19%), lukS-PVL (31.4%), lukF-PV (18.0%), lukE-lukD (16.3%), edin (3.2%), hla (16.3%), hlb (18.0%), hld (14.7%), hlg (22.9%), SCCmecI (16.3%), SCCmecII (22.9%), SCCmecIII (36.0%), SCCmecIV (21.3%), and SCCmecV (16.3%). Quantitative real-time PCR showed overexpression of mecRI and mecI in the toxigenic isolates. Moreover, RNAIII and sarA genes were the highest expressions of MRSA strains. The multi-locus sequence typing data confirmed a high prevalence of CC5, CC8, and CC30. However, ST30, ST22, and ST5 were the most prevalent in the resistant and toxigenic strains. Conclusion We demonstrated that although regulation of β-lactamase gene expressions is a significant contributor to resistance development, two-component systems also influence antibiotic resistance development in MRSA-BSI isolates. This indicates that resistant strains might have pathogenic potential. We also confirmed that some MLST types are more successful colonizers with a potential for MRSA-BSI.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Amir Hossein Hasani Fard ◽  
Hanieh Jalali ◽  
Homa Mohseni Kouchesfehani

Background: Cholestasis is a pathophysiological condition, significantly reducing spermatozoa production. MiR-34c is highly expressed in adult male testicles and controls different stages of spermatogenesis. Objectives: Here, we aimed to investigate miR-34c expression in the testes of rat models of cholestasis. The expressions of THY-1, FGF-2, and CASP-3 genes, that are targeted by mirR-34c were also investigated. Methods: Cholestasis was induced in six adult rats via bile duct ligation. Four weeks after cholestasis induction, sera and testicular tissues were collected for further examinations. The levels of liver enzymes were measured using the ELISA. The structure of the testes was evaluated by histological examination. Total RNA was extracted from testes using a special kit and converted to cDNA. The expressions of miR-34c-5p, THY-1, FGF-2, and CASP-3 genes were determined by Real-Time PCR. Results: The serum levels of ALP, AST, and ALT were significantly elevated in the rat models of cholestasis (P < 0.001). Real-Time PCR revealed that the expressions of miR-34c-5p, THY-1, and FGF-2 genes decreased while CASP-3 gene was upregulated in the testes of cholestatic animals (all differences were significant at P < 0.05). Conclusions: Our study indicated that cholestasis was associated with reduced expression of miR-34c and altered expression of its target genes in the testis. Our results highlight the potential effects of cholestasis, a hepatobiliary disease, on testicular tissue function and male fertility.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dario Lunni ◽  
Goffredo Giordano ◽  
Francesca Pignatelli ◽  
Carlo Filippeschi ◽  
Stefano Linari ◽  
...  

Abstract A real-time tool to monitor the electrospinning process is fundamental to improve the reproducibility and quality of the resulting nanofibers. Hereby, a novel optical system integrated through coaxial needle is proposed as monitoring tool for electrospinning process. An optical fiber (OF) is inserted in the inner needle, while the external needle is used to feed the polymeric solution (PEO/water) drawn by the process. The light exiting the OF passes through the solution drop at the needle tip and gets coupled to the electrospun fiber (EF) while travelling towards the nanofibers collector. Numerical and analytical models were developed to assess the feasibility and robustness of the light coupling. Experimental tests demonstrated the influence of the process parameters on the EF waveguide properties, in terms of waveguide length (L), and on the nanofibers diameter distribution, in terms of mean $$\widehat{D}$$ D ^ and normalized standard deviation $$\chi$$ χ . Data analysis reveals good correlation between L and $$\widehat{D}, \chi$$ D ^ , χ (respectively maximum correlation coefficients of $${\rho }_{L,\widehat{D}}$$ ρ L , D ^ = 0.88 and $${\rho }_{L,\chi }$$ ρ L , χ = 0.84), demonstrating the potential for effectively using the proposed light-assisted technology as real-time visual feedback on the process. The developed system can provide an interesting option for monitoring industrial electrospinning systems using multi- or moving needles with impact in the scaling-up of innovative nanofibers for soft systems.


2016 ◽  
Vol 38 (2) ◽  
pp. 427-448 ◽  
Author(s):  
Yanping Gao ◽  
Bing Feng ◽  
Siqi Han ◽  
Kai Zhang ◽  
Jing Chen ◽  
...  

Cancer remains one of the most threatening causes of human health impairment, and the mechanisms underlying tumorigenesis have not been completely characterized. MicroRNAs (miRNAs) are a group of endogenous, small (18∼25 nucleotides) non-coding RNAs which negatively regulate gene expressions by directly binding to the 3'-untranslated regions (3'-UTRs) of the target messenger RNAs (mRNAs). Increasing evidence has demonstrated abnormal miRNA profiles and confirmed their involvement in tumor initiation and progression. As one important member of the miR-200 family, microRNA (miR)-141 is aberrantly expressed in many human malignant tumors, participating in various cellular processes including epithelial-mesenchymal transition (EMT), proliferation, migration, invasion, and drug resistance. In the present review, we briefly describe the mechanisms underlying miR-141-mediated tumorigenesis and the possible future of miR-141 as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Binbing Ling ◽  
Lifeng Chen ◽  
Qiang Liu ◽  
Jian Yang

Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genesPIK3C3,PIM3, andPTENwere correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations(0.68≤r≤1.0)were observed betweenPIK3C3andPIM3in breast cancer, betweenPIK3C3andPTENin breast and ovary cancers, and betweenPIM3andPTENin breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.


2017 ◽  
Vol 4 (3) ◽  
pp. e337 ◽  
Author(s):  
Sundararajan Srinivasan ◽  
Marco Di Dario ◽  
Alessandra Russo ◽  
Ramesh Menon ◽  
Elena Brini ◽  
...  

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sajid Muhammad ◽  
Jingai Tan ◽  
Pingchuan Deng ◽  
Tingting Li ◽  
Haohua He ◽  
...  

Abstract Background Agricultural insects are one of the major threats to crop yield. It is a known fact that pesticide application is an extensive approach to eliminate insect pests, and has severe adverse effects on environment and ecosystem; however, there is lack of knowledge whether it could influence the physiology and metabolic processes in plants. Results Here, we systemically analyzed the transcriptomic changes in rice after a spray of two commercial pesticides, Abamectin (ABM) and Thiamethoxam (TXM). We found only a limited number of genes (0.91%) and (1.24%) were altered by ABM and TXM respectively, indicating that these pesticides cannot dramatically affect the performance of rice. Nevertheless, we characterized 1140 Differentially Expressed Genes (DEGs) interacting with 105 long non-coding RNAs (lncRNAs) that can be impacted by the two pesticides, suggesting their certain involvement in response to farm chemicals. Moreover, we detected 274 alternative splicing (AS) alterations accompanied by host genes expressions, elucidating a potential role of AS in control of gene transcription during insecticide spraying. Finally, we identified 488 transposons that were significantly changed with pesticides treatment, leading to a variation in adjacent coding or non-coding transcripts. Conclusion Altogether, our results provide valuable insights into pest management through appropriate timing and balanced mixture, these pesticides have no harmful effects on crop physiology over sustainable application of field drugs.


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