MicroRNAs and their role in hematological malignant diseases

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.

Open Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 180212 ◽  
Author(s):  
Bing Chen ◽  
Zijing Xia ◽  
Ya-Nan Deng ◽  
Yanfang Yang ◽  
Peng Zhang ◽  
...  

MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction. Along with analytical technique improvements in miRNA research, use of the emerging extracellular miRNAs is feasible for CRC diagnosis and prognosis.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3179-3179
Author(s):  
Chun-Liang Chen ◽  
Harkness Connell ◽  
Ira Racoma ◽  
Brandi Regula ◽  
Katherine Foley ◽  
...  

Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Several chromosomal translocations have prognostic significance and are used to classify patients for risk-directed therapy. The translocation t(1;19) which results in the fusion of TCF3 (E2A) and PBX1 genes occurs in 5% of pediatric ALL. E2A-PBX1 has been shown previously to have transcriptional activity. However, very little is known about what genes have altered expression in the presence of E2A-PBX1. To explore this question, we assessed genome wide gene expression after siRNA mediated knock down of E2A-PBX1. An E2A-PBX1 containing cell line (697) was transfected with E2A-PBX1 specific siRNA utilizing an Amaxa nucleofector2. Biologic replicates were performed by transfection of independent cultures. 70–80% reduction of E2A-PBX1 at mRNA and protein levels in 697 cells was reproducibly achieved using nucleofection and a combination of E2A-PBX1 specific siRNAs. Genome wide gene expression was assessed by Affymetrix U133 2.0 Plus arrays. Hybridizations were prepared and performed according to current Affymetrix protocols in the Functional Genomics Core at the Research Institute. Microarray data was normalized with RMA. Differentially expressed genes were selected using Significance Analysis of Microarrays (SAM). 78 probe sets demonstrated change in expression in E2A-PBX1 siRNA mediated knockdown relative to both mock transfection and nontargeting siRNA controls at a FDR of ≤ 5%. The 78 probe sets represent 49 known genes and 8 ESTs. Genes of specific interest upregulated by E2A-PBX1 include WNT-16, ANKS1B(EB-1), FAT, and RORB. Other investigators have previously cloned these genes by representational differential display from E2A-PBX1 expressing cell lines. We confirmed knockdown of these messages by E2A-PBX1 siRNA using qRT-PCR. Gene expression was calculated using the ΔΔCt method and normalization to ABL. Additionally, these genes are part of the E2A-PBX1 gene expression profile derived from primary pediatric leukemia samples previously published. [Ross, Blood 2003] An additional 34 candidate genes were further verified using qRT-PCR. The direction of change in gene expression correlated with microarray results in 30/34 genes evaluated. Other classes of genes upregulated by E2A-PBX1: kinases (FGFR2, MAP3K1), phosphtases (PPPIR14C), transcription factors (FOSL2, IRX2, EBF3, BMI1, BCL6), cell cycle-related genes (FBXW7, ETV5), Ras and Rho family genes (RAB8B). While B cell surface antigen expression (HLA-DRA, CD22) was decreased by E2A-PBX1. We have utilized siRNA to E2A-PBX1 to identify potential target genes of E2A-PBX1. This data suggests E2A-PBX1 can alter expression of a variety of classes of genes. Some of these genes may be potential targets for molecularly targeted therapy.


2021 ◽  
Vol 22 (9) ◽  
pp. 4697
Author(s):  
Alessio Ardizzone ◽  
Giovanna Calabrese ◽  
Michela Campolo ◽  
Alessia Filippone ◽  
Dario Giuffrida ◽  
...  

Cancer is a multifactorial disease that affects millions of people every year and is one of the most common causes of death in the world. The high mortality rate is very often linked to late diagnosis; in fact, nowadays there are a lack of efficient and specific markers for the early diagnosis and prognosis of cancer. In recent years, the discovery of new diagnostic markers, including microRNAs (miRNAs), has been an important turning point for cancer research. miRNAs are small, endogenous, non-coding RNAs that regulate gene expression. Compelling evidence has showed that many miRNAs are aberrantly expressed in human carcinomas and can act with either tumor-promoting or tumor-suppressing functions. miR-19a is one of the most investigated miRNAs, whose dysregulated expression is involved in different types of tumors and has been potentially associated with the prognosis of cancer patients. The aim of this review is to investigate the role of miR-19a in cancer, highlighting its involvement in cell proliferation, cell growth, cell death, tissue invasion and migration, as well as in angiogenesis. On these bases, miR-19a could prove to be truly useful as a potential diagnostic, prognostic, and therapeutic marker.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2979
Author(s):  
Paulína Pidíková ◽  
Iveta Herichová

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fu-jia Ren ◽  
Yao Yao ◽  
Xiao-yu Cai ◽  
Guo-ying Fang

MicroRNAs (miRNAs) are a type of small non-coding RNAs that play an essential role in numerous biological processes by regulating the post-transcriptional expression of target genes. Recent studies have demonstrated that miR-192-5p, a member of the miR-192 family, partakes in several human diseases, especially various cancers, including cancers of the lung, liver, and breast. Importantly, the levels of miR-192-5p are abundant in biofluids, including the serum and urine, and the exosomal levels of miR-192-5p in circulation can aid in the diagnosis and prognosis of various diseases, such as chronic hepatitis B (CHB) infection disease. Notably, recent studies suggest that miR-192-5p is regulated by long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there are no comprehensive overviews on the role of miR-192-5p in human diseases. This review discusses the significant studies on the role of miR-192-5p in various human diseases, with special emphasis on the diseases of the respiratory and digestive systems.


Author(s):  
Qingyuan Zheng ◽  
Xiao Yu ◽  
Menggang Zhang ◽  
Shuijun Zhang ◽  
Wenzhi Guo ◽  
...  

Long non-coding RNAs (lncRNA), as key regulators of cell proliferation and death, are involved in the regulation of various processes in the nucleus and cytoplasm, involving biological developmental processes in the fields of immunology, neurobiology, cancer, and stress. There is great scientific interest in exploring the relationship between lncRNA and tumors. Many researches revealed that lymph enhancer-binding factor 1-antisense RNA 1 (LEF1-AS1), a recently discovered lncRNA, is downregulated in myeloid malignancy, acting mainly as a tumor suppressor, while it is highly expressed and carcinogenic in glioblastoma (GBM), lung cancer, hepatocellular carcinoma (HCC), osteosarcoma, colorectal cancer (CRC), oral squamous cell carcinoma (OSCC), prostatic carcinoma, retinoblastoma, and other malignant tumors. Furthermore, abnormal LEF1-AS1 expression was associated with tumorigenesis, development, survival, and prognosis via the regulation of target genes and signaling pathways. This review summarizes the existing data on the expression, functions, underlying mechanism, relevant signaling pathways, and clinical significance of LEF1-AS1 in cancer. It is concluded that LEF1-AS1 can serve as a novel biomarker for the diagnosis and prognosis of various tumors, thus deserves further attention in the future.


2016 ◽  
Vol 3 (1) ◽  
Author(s):  
YASIN JESHIMA KHAN ◽  
HUSNARA Tyagi ◽  
Anil kumar Singh ◽  
Santosh kumar. Magadum

Plants respond through a cascade of reactions resulting in varied cellular environment leading to alterations in the patterns of protein expression resulting in phonotypic changes. Single cell genomics and global proteomics came out to be powerful tools and efficient techniques in studying stress tolerant plants. Non-coding RNAs are a distinct class of regulatory RNAs in plants and animals that control a variety of biological processes. Small ncRNAs play a vital role in post transcriptional gene regulation by either translational repression or by inducing mRNA cleavage. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs control the expression of cognate target genes by binding to complementary sequences, resulting in cleavage or translational inhibition of the target RNAs. siRNAs too have a similar structure, function, and biogenesis like miRNAs but are derived from long double-stranded RNAs and can often direct DNA methylation at target sequences.In this review, we focus on the involvement of ncRNAs in comabting abiotic stresses of soybean. This review emphasis on previously known miRNAs as they play important role in several abiotic stresses like drought, salinity, chilling and heat stress by their diverse roles in mediating biological processes like gene expression, chromatin formation, defense of genome against invading viruses. This review attempts to elucidate the various kinds of non-coding RNAs explored, their discovery, biogenesis, functions, and response for different type of abiotic stresses and future aspects for crop improvement in the context of soybean, a representative grain legume.


Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1483
Author(s):  
Ivan Antonov ◽  
Yulia Medvedeva

Although thousands of mammalian long non-coding RNAs (lncRNAs) have been reported in the last decade, their functional annotation remains limited. A wet-lab approach to detect functions of a novel lncRNA usually includes its knockdown followed by RNA sequencing and identification of the deferentially expressed genes. However, identification of the molecular mechanism(s) used by the lncRNA to regulate its targets frequently becomes a challenge. Previously, we developed the ASSA algorithm that detects statistically significant inter-molecular RNA-RNA interactions. Here we designed a workflow that uses ASSA predictions to estimate the ability of an lncRNA to function via direct base pairing with the target transcripts (co- or post-transcriptionally). The workflow was applied to 300+ lncRNA knockdown experiments from the FANTOM6 pilot project producing statistically significant predictions for 71 unique lncRNAs (104 knockdowns). Surprisingly, the majority of these lncRNAs were likely to function co-transcriptionally, i.e., hybridize with the nascent transcripts of the target genes. Moreover, a number of the obtained predictions were supported by independent iMARGI experimental data on co-localization of lncRNA and chromatin. We detected an evolutionarily conserved lncRNA CHASERR (AC013394.2 or LINC01578) that could regulate target genes co-transcriptionally via interaction with a nascent transcript by directing CHD2 helicase. The obtained results suggested that this nuclear lncRNA may be able to activate expression of the target genes in trans by base-pairing with the nascent transcripts and directing the CHD2 helicase to the regulated promoters leading to open the chromatin and active transcription. Our study highlights the possible importance of base-pairing between nuclear lncRNAs and nascent transcripts for the regulation of gene expression.


Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 417
Author(s):  
Ha Thi Nguyen ◽  
Salah Eddine Oussama Kacimi ◽  
Truc Ly Nguyen ◽  
Kamrul Hassan Suman ◽  
Roselyn Lemus-Martin ◽  
...  

MicroRNAs (miRNAs) are small non-coding RNAs. They can regulate the expression of their target genes, and thus, their dysregulation significantly contributes to the development of cancer. Growing evidence suggests that miRNAs could be used as cancer biomarkers. As an oncogenic miRNA, the roles of miR-21 as a diagnostic and prognostic biomarker, and its therapeutic applications have been extensively studied. In this review, the roles of miR-21 are first demonstrated via its different molecular networks. Then, a comprehensive review on the potential targets and the current applications as a diagnostic and prognostic cancer biomarker and the therapeutic roles of miR-21 in six different cancers in the digestive system is provided. Lastly, a brief discussion on the challenges for the use of miR-21 as a therapeutic tool for these cancers is added.


2021 ◽  
Vol 10 (10) ◽  
pp. 2219
Author(s):  
Monika Prill ◽  
Agnieszka Karkucinska-Wieckowska ◽  
Magdalena Lebiedzinska-Arciszewska ◽  
Giampaolo Morciano ◽  
Agata Charzynska ◽  
...  

Numerous papers have reported altered expression patterns of Ras and/or ShcA proteins in different types of cancers. Their level can be potentially associated with oncogenic processes. We analyzed samples of pediatric brain tumors reflecting different groups such as choroid plexus tumors, diffuse astrocytic and oligodendroglial tumors, embryonal tumors, ependymal tumors, and other astrocytic tumors as well as tumor malignancy grade, in order to characterize the expression profile of Ras, TrkB, and three isoforms of ShcA, namely, p66Shc, p52Shc, and p46Shc proteins. The main aim of our study was to evaluate the potential correlation between the type of pediatric brain tumors, tumor malignancy grade, and the expression patterns of the investigated proteins.


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