scholarly journals Regulatory Functions of MicroRNAs in Cancer Pathogenesis

Author(s):  
Mahafarin Maralani ◽  
Behzad Baradaran ◽  
Khalil Hajiasgharzadeh ◽  
Marc Peeters

MicroRNAs (miRNAs) are a large family of evolutionary conserved small non-coding RNA molecules that firstly discovered in 1993. They regulate gene expression of about 50% of protein-coding genes at the post-transcriptional level. MiRNAs can target numerous messenger RNAs and subsequent misexpression of them can affect many different signaling pathways. They are playing a pivotal role in cancer development by regulation of the genes expression which involved in the proliferation, survival, differentiation, apoptosis or metastasis of the cancer cells. Several treatment approaches such as inhibition of oncomiRs and restoration of tumor suppressor miRNAs have been established in certain types of cancers and some other miRNA-based strategies are in development for cancer prevention and treatment. Nowadays, cancer is the most important target of miRNA therapeutics and the specific mechanisms by which miRNA mediates cancer pathways needs more research and study

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Jin-yan Wang ◽  
Qian Zhang ◽  
Dan-dan Wang ◽  
Wei Yan ◽  
Huan-huan Sha ◽  
...  

MiRNAs, small non-coding RNA molecules, were recognized to be associated with the incidence and development of diverse neoplasms. MiRNAs were small non-coding RNAs that could regulate post-transcriptional level by binding to 3′-UTR of target mRNAs. Amongst which, miR-29a was demonstrated that it had significant impact on oncogenicity in various neoplasms through binding to critical genes which enhanced or inhibited the progression of cancers. MiR-29a participated in kinds of physiological and pathological processes, including virus replication, cell proliferation, differentiation, apoptosis, fibrosis, angiogenesis, tumorigenicity, metastasis, drug-resistance, and so on. According to its sufficient sensitivity and specificity, many studies showed that miR-29a might serve as a potential therapeutic target and promising biomarker in various tumors. In this review, we discussed the functions of miR-29a and its potential application in the diagnosis, treatment and stages of carcinoma, which could provide additional insight to develop a novel therapeutic strategy.


2021 ◽  
Author(s):  
Gábor Torma ◽  
Dóra Tombácz ◽  
Norbert Moldován ◽  
Ádám Fülöp ◽  
István Prazsák ◽  
...  

Abstract In this study, we used two long-read sequencing (LRS) techniques, Sequel from the Pacific Biosciences and MinION from Oxford Nanopore Technologies, for the transcriptional characterization of a prototype baculovirus, Autographacalifornica multiple nucleopolyhedrovirus. LRS is able to read full-length RNA molecules, and thereby to distinguish between transcript isoforms, mono- and polycistronic RNAs, and overlapping transcripts. Altogether, we detected 875 transcripts, of which 759 are novel and 116 have been annotated previously. These RNA molecules include 41 novel putative protein coding transcript (each containing 5’-truncated in-frame ORFs), 14 monocistronic transcripts, 99 multicistronic RNAs, 101 non-coding RNA, and 504 length isoforms. We also detected RNA methylation in 12 viral genes and RNA hyper-editing in the longer 5’-UTR transcript isoform of ORF 19 gene.


2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Andrea Feliciano ◽  
Beatriz Sánchez-Sendra ◽  
Hiroshi Kondoh ◽  
Matilde E. LLeonart

MicroRNAs (miRNAs) are small (approximately 22 nt) noncoding endogenous RNA molecules that regulate gene expression and protein coding by base pairing with the3′untranslated region (UTR) of target mRNAs. miRNA expression is associated with cancer pathogenesis because miRNAs are intimately linked to cancer development. Senescence blocks cell proliferation, representing an important barrier that cells must bypass to reach malignancy. Importantly, certain miRNAs have been shown to have an important role during cellular senescence, which is also involved in human tumorigenesis. Therefore, therapeutic induction of senescence by drugs or miRNA-based therapies is a potential method to treat cancer by inducing a persistent growth arrest in tumors.


2021 ◽  
Author(s):  
Hanneke Vlaming ◽  
Claudia A Mimoso ◽  
Benjamin JE Martin ◽  
Andrew R Field ◽  
Karen Adelman

Organismal growth and development rely on RNA Polymerase II (RNAPII) synthesizing the appropriate repertoire of messenger RNAs (mRNAs) from protein-coding genes. Productive elongation of full-length transcripts is essential for mRNA function, however what determines whether an engaged RNAPII molecule will terminate prematurely or transcribe processively remains poorly understood. Notably, despite a common process for transcription initiation across RNAPII-synthesized RNAs, RNAPII is highly susceptible to termination when transcribing non-coding RNAs such as upstream antisense RNAs (uaRNAs) and enhancers RNAs (eRNAs), suggesting that differences arise during RNAPII elongation. To investigate the impact of transcribed sequence on elongation potential, we developed a method to screen the effects of thousands of INtegrated Sequences on Expression of RNA and Translation using high-throughput sequencing (INSERT-seq). We found that higher AT content in uaRNAs and eRNAs, rather than specific sequence motifs, underlies the propensity for RNAPII termination on these transcripts. Further, we demonstrate that 5' splice sites exert both splicing-dependent and autonomous, splicing-independent stimulation of transcription, even in the absence of polyadenylation signals. Together, our results reveal a potent role for transcribed sequence in dictating gene output at mRNA and non-coding RNA loci, and demonstrate the power of INSERT-seq towards illuminating these contributions.


MicroRNAs (miRNAs or miRs) are a type of non-coding RNA molecules that regulate the gene expression in a negative way, by downregulating the gene expression mainly at the post-transcriptional level, either by the mRNA degradation process or the inhibition of the translation. The role that many miRNAs play in the pathogenesis of several diseases is well known, such as in the inflammation process, in several steps of the oncogenesis or the metabolism of several virus and bacteria among many others. One of the main limitations in the therapeutic use of miRNAs is the ability to reach the target, as well as doing so without causing any collateral damage. One microRNA can indeed regulate up to 200 target-genes, and one gene can be influenced by a lot of different microRNAs. This is the purpose of the Bio Immune(G)ene Medicine: to achieve the cell without harm, use all the molecular resources available, especially epigenetic with the microRNAs, and to restore the cell homeostasis. The Bio Immune(G)ene Medicine only seeks to play a regulatory biomimetic role, to give the cell the needed information for its own right regulation. Our experience in cell regulation for the past few years has shown the way to fight, for instance, against the deleterious effects of viruses or bacteria in the lymphocytes, also at the background of many autoimmune or allergic diseases, as well as to regulate many other pathological processes. To fulfil this purpose, nanobiotechnology is used to reach the targets; we thus introduce very low doses of miRNAs in nano compounds with the aim to promote the regulation of the main signalling pathways disturbed in a given pathology.


2017 ◽  
Author(s):  
Weibing Yang ◽  
Raymond Wightman ◽  
Elliot M. Meyerowitz

AbstractIn eukaryotic cells, most RNA molecules are exported into the cytoplasm after being transcribed in the nucleus. Long noncoding RNAs (lncRNAs) have been found to reside and function primarily inside the nucleus, but nuclear localization of protein-coding messenger RNAs (mRNAs) has been considered rare in both animals and plants. Here we show that two mRNAs, transcribed from theCDC20andCCS52B(plant orthologue ofCDH1) genes, are specifically sequestered inside the nucleus during the cell cycle. CDC20 and CDH1 both function as coactivators of the anaphase-promoting complex or cyclosome (APC/C) E3 ligase to trigger cyclin B (C YCB) destruction. In theArabidopsis thalianashoot apical meristem (SAM), we findCDC20andCCS52Bare co-expressed withCYCBsin mitotic cells.CYCBtranscripts can be exported and translated, whereasCDC20andCCS52BmRNAs are strictly confined to the nucleus at prophase and the cognate proteins are not translated until the redistribution of the mRNAs to the cytoplasm after nuclear envelope breakdown (NEBD) at prometaphase. The 5’ untranslated region (UTR) is necessary and sufficient forCDC20mRNA nuclear localization as well as protein translation. Mitotic enrichment ofCDC20andCCS52Btranscripts enables the timely and rapid activation of APC/C, while their nuclear sequestration at prophase appears to protect cyclins from precocious degradation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clara Ibel Chamorro ◽  
Jesper Eisfeldt ◽  
Oliver Willacy ◽  
Nikolai Juul ◽  
Magdalena Fossum

AbstractUrinary bladder wound healing relies on multiple biological events that are finely tuned in a spatial–temporal manner. MicroRNAs are small non-coding RNA molecules with regulatory functions. We hypothesized that microRNAs are important molecules in the coordination of normal urinary bladder wound healing. We aimed at identifying microRNAs expressed during bladder wound healing using Affymetrix global array for microRNA profiling of the rodent urinary bladder during healing of a surgically created wound. Results were validated in the rat bladders by real-time PCR (RT-PCR) using three of the differentially expressed (DE) microRNAs. The model was thereafter validated in human cells, by measuring the expression of eight of the DE microRNAs upon in vitro wound-healing assays in primary urothelial cells. Our results indicated that 508 (40%) of all rodent microRNAs were expressed in the urinary bladder during wound healing. Thirteen of these microRNAs (1%) were DE (false discovery rate (FDR) < 0.05, P < 0.05, |logfold|> 0.25) in wounded compared to non-wounded bladders. Bioinformatic analyses helped us to identify target molecules for the DE microRNAs, and biological pathways involved in tissue repair. All data are made available in an open-access database for other researchers to explore.


2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Wojciech Rosikiewicz ◽  
Izabela Makałowska

Natural antisense transcripts (NATs) are RNA molecules that originate from opposite DNA strands of the same genomic locus (cis-NAT) or unlinked genomic loci (trans-NAT). NATs may play various regulatory functions at the transcriptional level via transcriptional interference. NATs may also regulate gene expression levels post-transcriptionally via induction of epigenetic changes or double-stranded RNA formation, which may lead to endogenous RNA interference, RNA editing or RNA masking. The true biological significance of the natural antisense transcripts remains controversial despite many years of research. Here, we summarize the current state of knowledge and discuss the sense-antisense overlap regulatory mechanisms and their potential.


2020 ◽  
Vol 20 (16) ◽  
pp. 1883-1894
Author(s):  
Yuan-Rong Liu ◽  
Ping-Yu Wang ◽  
Ning Xie ◽  
Shu-Yang Xie

MicroRNAs (miRNAs) are short, non-coding RNA molecules that regulate gene expression by translational repression or deregulation of messenger RNAs. Accumulating evidence suggests that miRNAs play various roles in the development and progression of lung cancers. Although their precise roles in targeted cancer therapy are currently unclear, miRNAs have been shown to affect the sensitivity of tumors to anticancer drugs. A large number of recent studies have demonstrated that some anticancer drugs exerted antitumor activities by affecting the expression of miRNAs and their targeted genes. These studies have elucidated the specific biological mechanism of drugs in tumor suppression, which provides a new idea or basis for their clinical application. In this review, we summarized the therapeutic mechanisms of drugs in lung cancer therapy through their effects on miRNAs and their targeted genes, which highlights the roles of miRNAs as targets in lung cancer therapy.


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