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Open accessJournal ArticleDOI: 10.3390/IJMS22052561

MicroRNAs as Modulators of Oral Tumorigenesis—A Focused Review

04 Mar 2021-International Journal of Molecular Sciences (Multidisciplinary Digital Publishing Institute)-Vol. 22, Iss: 5, pp 2561
Abstract: Oral cancers constitute the majority of head and neck tumors, with a relatively high incidence and poor survival rate in developing countries. While the five-year survival rates of the oral cancer patients have increased to 65%, the overall survival for advanced stages has been at 27% for the past ten years, emphasizing the necessity for further understanding the etiology of the disease, diagnosis, and formulating possible novel treatment regimens. MicroRNAs (miRNAs), a family of small non-coding RNA, have emerged as master modulators of gene expression in various cellular and biological process. Aberrant expression of these dynamic molecules has been associated with many human diseases, including oral cancers. The deregulated miRNAs have been shown to control various oncogenic processes, including sustaining proliferative signaling, evading growth suppressors, resisting cell death activating invasion and metastasis, and inducing angiogenesis. Hence, the aberrant expression of miRNAs associated with oral cancers, makes them potential candidates for the investigation of functional markers, which will aid in the differential diagnosis, prognosis, and development of novel therapeutic regimens. This review presents a holistic insight into our understanding of the role of miRNAs in regulating various hallmarks of oral tumorigenesis.

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10 results found


Journal ArticleDOI: 10.1016/J.LFS.2021.119649
24 May 2021-Life Sciences
Abstract: Lung cancer (LC) is a leading cause of death worldwide with high mortality and morbidity A wide variety of risk factors are considered for LC development such as smoking, air pollution and family history It appears that genetic and epigenetic factors are also potential players in LC development and progression AMP-activated protein kinase (AMPK) is a signaling pathway with vital function in inducing energy balance and homeostasis An increase in AMP:ATP and ADP:ATP ratio leads to activation of AMPK signaling by upstream mediators such as LKB1 and CamKK Dysregulation of AMPK signaling is a common finding in different cancers, particularly LC AMPK activation can significantly enhance LC metastasis via EMT induction Upstream mediators such as PLAG1, IMPAD1, and TUFM can regulate AMPK-mediated metastasis AMPK activation can promote proliferation and survival of LC cells via glycolysis induction In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling This is due to double-edged sword role of AMPK signaling in LC cells Furthermore, AMPK signaling can regulate response of LC cells to chemotherapy and radiotherapy that are discussed in the current review

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Topics: AMPK (75%), Autophagy (50%)

7 Citations


Open accessJournal ArticleDOI: 10.1016/J.JFF.2021.104660
Elika Verma1, Aviral Kumar1, Uzini Devi Daimary1, Dey Parama1  +3 moreInstitutions (2)
Abstract: Cancer is one of the deadliest diseases worldwide which kills approximately 10 million people annually. Although, substantial improvements have been made in the treatment modalities of this disease, radio-resistance, chemo-resistance, and adverse side-effects limit their potential. It is now well-established that natural products provide a less toxic and efficacious alternative in developing drugs for the treatment of cancer. Hence, we investigated the potential of baicalein, a natural compound isolated from the roots of Scutelleria baicaleinsis, which targets wide spectrum of molecular alterations involved in the progression of cancer. At the molecular level, this compound has shown to exhibit anti-inflammatory and anti-cancerous properties via modulation of multiple cell signaling pathways and transcription factors, including PI3K/Akt/mTOR, Wnt/β-catenin, MAPK, NF-κB, Smad4, Notch 1/Hes, Nrf2/Keap 1, AMPK, Src/Id1, ROS signaling, miR 183/ezrin, and Shh signaling pathways. Overall, this review provides a strong evidence for the potential of baicalein as a therapeutic agent for the treatment of different malignancies.

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Topics: PI3K/AKT/mTOR pathway (55%), Baicalein (54%), Wnt signaling pathway (52%) ... read more

4 Citations


Journal ArticleDOI: 10.1002/IUB.2522
Sosmitha Girisa1, Queen Saikia1, Devivasha Bordoloi1, Kishore Banik1  +5 moreInstitutions (2)
01 Aug 2021-Iubmb Life
Abstract: Cancer is a major public health concern due to high mortality and poor quality of life of patients. Despite the availability of advanced therapeutic interventions, most treatment modalities are not efficacious, very expensive, and cause several adverse side effects. The factors such as drug resistance, lack of specificity, and low efficacy of the cancer drugs necessitate developing alternative strategies for the prevention and treatment of this disease. Xanthohumol (XN), a prenylated chalcone present in Hop (Humulus lupulus), has been found to possess prominent activities against aging, diabetes, inflammation, microbial infection, and cancer. Thus, this manuscript thoroughly reviews the literature on the anti-cancer properties of XN and its various molecular targets. XN was found to exert its inhibitory effect on the growth and proliferation of cancer cells via modulation of multiple signaling pathways such as Akt, AMPK, ERK, IGFBP2, NF-κB, and STAT3, and also modulates various proteins such as Notch1, caspases, MMPs, Bcl-2, cyclin D1, oxidative stress markers, tumor-suppressor proteins, and miRNAs. Thus, these reports suggest that XN possesses enormous therapeutic potential against various cancers and could be potentially used as a multi-targeted anti-cancer agent with minimal adverse effects.

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Topics: Xanthohumol (55%), Cancer prevention (53%), Cancer (51%)

3 Citations


Journal ArticleDOI: 10.1002/JCP.30463
Krishan Kumar Thakur1, Aviral Kumar1, Kishore Banik1, Elika Verma1  +5 moreInstitutions (3)
Abstract: In recent years, triple-negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%-24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease-free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms.

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3 Citations


Open accessJournal ArticleDOI: 10.3389/FNANO.2021.694838
09 Jun 2021-
Abstract: Cancer is a significant health hazard of the 21st century, and GLOBOCAN predicts increasing cancer incidence in the coming decades. Though several conventional treatment modalities exist, most of them end up causing off-target and debilitating effects, and drug resistance acquisition. Advances in our understanding of tumor molecular biology offer alternative strategies for precise, robust, and potentially less toxic treatment paradigms for circumventing the disease at the cellular and molecular level. Several deregulated molecules associated with tumorigenesis have been developed as targets in RNA interference (RNAi) based cancer therapeutics. RNAi, a post-transcriptional gene regulation mechanism, has significantly gained attention because of its precise multi-targeted gene silencing. Although the RNAi approach is favorable, the direct administration of small oligonucleotides has not been fruitful because of their inherent lower half-lives and instability in the biological systems. Moreover, the lack of an appropriate delivery system to the primary site of the tumor that helps determine the potency of the drug and its reach, has limited the effective medical utilization of these bio-drugs. Nanotechnology, with its unique characteristics of enhanced permeation and better tumor-targeting efficiency, offers promising solutions owing to the various possibilities and amenability for modifications of the nanoparticles to augment cancer therapeutics. Nanoparticles could be made multimodal, by designing and synthesizing multiple desired functionalities, often resulting in unique and potentially applicable biological structures. A small number of Phase 1 clinical trials with systemically administered siRNA molecules conjugated with nanoparticles have been completed and the results are promising, indicating that, these new combinatorial therapies can successfully and safely be used to inhibit target genes in cancer patients to alleviate some of the disease burden. In this review, we highlight different types of nano-based delivery strategies for engineering Nano-RNAi-based bio drugs. Furthermore, we have highlighted the insights gained from current research that are entering the preclinical evaluation and information about initial clinical developments, shaping the future for next generation cancer therapeutics.

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Topics: Targeted drug delivery (51%)

2 Citations


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262 results found


Journal ArticleDOI: 10.1038/NRD.2016.246
Rajesha Rupaimoole1, Frank J. Slack1Institutions (1)
Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic. In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

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2,209 Citations


Open accessJournal ArticleDOI: 10.1101/GAD.1262504
Jinju Han1, Yoontae Lee, Kyu-Hyun Yeom, Young Kook Kim  +2 moreInstitutions (1)
Abstract: RNase III proteins play key roles in microRNA (miRNA) biogenesis. The nuclear RNase III Drosha cleaves primary miRNAs (pri-miRNAs) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic RNase III Dicer to generate mature miRNAs. While Dicer (class III) and other simple RNase III proteins (class I) have been studied intensively, the class II enzyme Drosha remains to be characterized. Here we dissected the action mechanism of human Drosha by generating mutants and by characterizing its new interacting partner, DGCR8. The basic action mechanism of Drosha was found to be similar to that of human Dicer; the RNase III domains A and B form an intramolecular dimer and cleave the 3 and 5 strands of the stem, respectively. Human Drosha fractionates at ∼650 kDa, indicating that Drosha functions as a large complex. In this complex, Drosha interacts with DGCR8, which contains two double-stranded RNA (dsRNA)-binding domains. By RNAi and biochemical reconstitution, we show that DGCR8 may be an essential component of the pri-miRNA processing complex, along with Drosha. Based on these results, we propose a model for the action mechanism of class II RNase III proteins.

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Topics: Drosha (74%), Dicer (68%), Microprocessor complex (67%) ... read more

1,927 Citations


Open accessJournal ArticleDOI: 10.1002/EMMM.201100209
Marilena V. Iorio, Carlo M. Croce1Institutions (1)
Abstract: Early studies have shown how aberrantly expressed microRNAs are a hallmark of several diseases like cancer. MicroRNA expression profiling was shown to be associated with tumour development, progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. Moreover, based on the increasing number of studies demonstrating that microRNAs can function as potential oncogenes or oncosuppressor genes, with the goal to improve disease response and increase cure rates, miRNA-based anticancer therapies have recently been exploited, either alone or in combination with current targeted therapies. The advantage of using microRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. Here, we review our current knowledge about the involvement of microRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.

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Topics: Cancer (51%)

1,366 Citations


Open accessJournal ArticleDOI: 10.1101/GAD.1074403
Abstract: MicroRNAs (miRNAs) are an abundant class of tiny RNAs thought to regulate the expression of protein-coding genes in plants and animals. In the present study, we describe a computational procedure to identify miRNA genes conserved in more than one genome. Applying this program, known as MiRscan, together with molecular identification and validation methods, we have identified most of the miRNA genes in the nematode Caenorhabditis elegans. The total number of validated miRNA genes stands at 88, with no more than 35 genes remaining to be detected or validated. These 88 miRNA genes represent 48 gene families; 46 of these families (comprising 86 of the 88 genes) are conserved in Caenorhabditis briggsae, and 22 families are conserved in humans. More than a third of the worm miRNAs, including newly identified members of the lin-4 and let-7 gene families, are differentially expressed during larval development, suggesting a role for these miRNAs in mediating larval developmental transitions. Most are present at very high steady-state levels-more than 1000 molecules per cell, with some exceeding 50,000 molecules per cell. Our census of the worm miRNAs and their expression patterns helps define this class of noncoding RNAs, lays the groundwork for functional studies, and provides the tools for more comprehensive analyses of miRNA genes in other species.

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Topics: Lin-4 microRNA precursor (59%), Caenorhabditis briggsae (57%), Gene family (54%) ... read more

1,340 Citations


Open accessJournal ArticleDOI: 10.3389/FENDO.2018.00402
Abstract: MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3' untranslated region (3' UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5' UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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1,128 Citations


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