Cucurbitacin mediated regulation of deregulated oncogenic signaling cascades and non-coding RNAs in different cancers: Spotlight on JAK/STAT, Wnt/β-catenin, mTOR, TRAIL-mediated pathways

2020 ◽  
Author(s):  
Xiukun Lin ◽  
Ammad Ahmad Farooqi
Keyword(s):  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Non Coding Rnas

MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic In-sights

2020 ◽  
Vol 20 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Evangelia Legaki ◽  
Maria Gazouli ◽  
Silvia Rinaldi ◽  
Rossana Berardi
Keyword(s):  
Molecular Biology ◽  
Detailed Analysis ◽  
Signaling Pathways ◽  
Individualized Medicine ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Non Coding Rnas ◽  
Oncogenic Signaling Pathways ◽  
Competitive Endogenous Rna

: Central dogma of molecular biology has remained cornerstone of classical molecular biology but serendipitous discovery of microRNAs (miRNAs) in nematodes paradigmatically shifted our current understanding of the intricate mech-anisms which occur during transitions from transcription to translation. Discovery of miRNA captured tremendous attention and appreciation and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets which are regulated by MALAT1 to stimulate or repress expression of tar-get genes. However, in this review our main focus is to summarize mechanistic insights related to MALAT1-mediated regu-lation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening however, there is still a need to identify additional mechanisms. MALAT1 is involved in multi-layered regulation of multiple transduction cascades and detailed analysis of different pathways will be helpful in getting a step closer to individualized medicine.

scholarly journals Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks

2020 ◽  
Vol 21 (21) ◽  
pp. 8018 ◽  
Author(s):  
Monica Sharma ◽  
Kevin Pruitt
Keyword(s):  
Stem Cell ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Cell Movement ◽  
Signaling Cascades ◽  
Cell Renewal ◽  
Oncogenic Signaling ◽  
Stem Cell Renewal ◽  
Development Processes ◽  
Cell Niche

The Wnt pathway is an integral cell-to-cell signaling hub which regulates crucial development processes and maintenance of tissue homeostasis by coordinating cell proliferation, differentiation, cell polarity, cell movement, and stem cell renewal. When dysregulated, it is associated with various developmental diseases, fibrosis, and tumorigenesis. We now better appreciate the complexity and crosstalk of the Wnt pathway with other signaling cascades. Emerging roles of the Wnt signaling in the cancer stem cell niche and drug resistance have led to development of therapeutics specifically targeting various Wnt components, with some agents currently in clinical trials. This review highlights historical and recent findings on key mediators of Wnt signaling and how they impact antitumor immunity and maintenance of cancer stem cells. This review also examines current therapeutics being developed that modulate Wnt signaling in cancer and discusses potential shortcomings associated with available therapeutics.

scholarly journals Oncogenic Signaling in Tumorigenesis and Applications of siRNA Nanotherapeutics in Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 632 ◽  
Author(s):  
Nur Izyani Kamaruzman ◽  
Noraini Abd Aziz ◽  
Chit Laa Poh ◽  
Ezharul Hoque Chowdhury
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Targeted Delivery ◽  
Therapeutic Strategies ◽  
Signaling Cascades ◽  
Breast Tumorigenesis ◽  
Oncogenic Signaling ◽  
Complementary Sequence ◽  
Genetic Manipulations ◽  
Oncogene Products

Overexpression of oncogenes and cross-talks of the oncoproteins-regulated signaling cascades with other intracellular pathways in breast cancer could lead to massive abnormal signaling with the consequence of tumorigenesis. The ability to identify the genes having vital roles in cancer development would give a promising therapeutics strategy in combating the disease. Genetic manipulations through siRNAs targeting the complementary sequence of the oncogenic mRNA in breast cancer is one of the promising approaches that can be harnessed to develop more efficient treatments for breast cancer. In this review, we highlighted the effects of major signaling pathways stimulated by oncogene products on breast tumorigenesis and discussed the potential therapeutic strategies for targeted delivery of siRNAs with nanoparticles in suppressing the stimulated signaling pathways.

Antimetastatic effects of Citrus-derived bioactive ingredients: Mechanistic insights

2021 ◽  
Vol 67 (2) ◽  
pp. 178-186
Author(s):  
Ammad Ahmad Farooqi ◽  
Fatima Tahir ◽  
Maham Fakhar ◽  
Ghazala Butt ◽  
Tatiana Colombo Pimentel ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Signaling Cascades ◽  
Citrus Fruits ◽  
Bioactive Components ◽  
Oncogenic Signaling ◽  
Oncogenic Pathways ◽  
Metastasis Research ◽  
Bioactive Ingredients ◽  
Underlying Mechanisms ◽  
Shed Light

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

scholarly journals Pancreatic oncogenic signaling cascades converge at Protein Kinase D1

Cell Cycle ◽  
2015 ◽  
Vol 14 (10) ◽  
pp. 1489-1490 ◽  
Author(s):  
Geou-Yarh Liou ◽  
Michael Leitges ◽  
Peter Storz
Keyword(s):  
Protein Kinase ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Protein Kinase D1

scholarly journals EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 951 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Marina Pinheiro ◽  
Andreia Granja ◽  
Fulvia Farabegoli ◽  
Salette Reis ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Dna Methyltransferases ◽  
Oncogenic Signaling ◽  
New Horizons ◽  
Sequencing Technologies ◽  
Preclinical Trials ◽  
Non Coding Rnas ◽  
Notch Pathways ◽  
Oncogenic Signaling Pathways

Decades of research have enabled us to develop a better and sharper understanding of multifaceted nature of cancer. Next-generation sequencing technologies have leveraged our existing knowledge related to intra- and inter-tumor heterogeneity to the next level. Functional genomics have opened new horizons to explore deregulated signaling pathways in different cancers. Therapeutic targeting of deregulated oncogenic signaling cascades by products obtained from natural sources has shown promising results. Epigallocatechin-3-gallate (EGCG) has emerged as a distinguished chemopreventive product because of its ability to regulate a myriad of oncogenic signaling pathways. Based on its scientifically approved anticancer activity and encouraging results obtained from preclinical trials, it is also being tested in various phases of clinical trials. A series of clinical trials associated with green tea extracts and EGCG are providing clues about significant potential of EGCG to mechanistically modulate wide ranging signal transduction cascades. In this review, we comprehensively analyzed regulation of JAK/STAT, Wnt/β-catenin, TGF/SMAD, SHH/GLI, NOTCH pathways by EGCG. We also discussed most recent evidence related to the ability of EGCG to modulate non-coding RNAs in different cancers. Methylation of the genome is also a widely studied mechanism and EGCG has been shown to modulate DNA methyltransferases (DNMTs) and protein enhancer of zeste-2 (EZH2) in multiple cancers. Moreover, the use of nanoformulations to increase the bioavailability and thus efficacy of EGCG will be also addressed. Better understanding of the pleiotropic abilities of EGCG to modulate intracellular pathways along with the development of effective EGCG delivery vehicles will be helpful in getting a step closer to individualized medicines.

scholarly journals Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies

2008 ◽  
Vol 29 (2) ◽  
pp. 234-252 ◽  
Author(s):  
Murielle Mimeault ◽  
Parmender P. Mehta ◽  
Ralph Hauke ◽  
Surinder K. Batra
Keyword(s):  
Progenitor Cells ◽  
Cancer Progression ◽  
Prostatic Cancer ◽  
Molecular Mechanisms ◽  
Prostate Gland ◽  
Cancer Recurrence ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Beneficial Effects ◽  
Stromal Cell Derived Factor

Abstract This review summarizes the recent advancements that have improved our understanding of the functions of prostatic stem/progenitor cells in maintaining homeostasis of the prostate gland. We also describe the oncogenic events that may contribute to their malignant transformation into prostatic cancer stem/progenitor cells during cancer initiation and progression to metastatic disease stages. The molecular mechanisms that may contribute to the intrinsic or the acquisition of a resistant phenotype by the prostatic cancer stem/progenitor cells and their differentiated progenies with a luminal phenotype to the current therapies and disease relapse are also reviewed. The emphasis is on the critical functions of distinct tumorigenic signaling cascades induced through the epidermal growth factor system, hedgehog, Wnt/β-catenin, and/or stromal cell-derived factor-1/CXC chemokine receptor-4 pathways as well as the deregulated apoptotic signaling elements and ATP-binding cassette multidrug transporter. Of particular therapeutic interest, we also discuss the potential beneficial effects associated with the targeting of these signaling elements to overcome the resistance to current treatments and prostate cancer recurrence. The combined targeted strategies toward distinct oncogenic signaling cascades in prostatic cancer stem/progenitor cells and their progenies as well as their local microenvironment, which could improve the efficacy of current clinical chemotherapeutic treatments against incurable, androgen-independent, and metastatic prostate cancers, are also described.

scholarly journals Decoding the Oncogenic Signals from the Long Non-Coding RNAs

Onco ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 176-206
Author(s):  
Revathy Nadhan ◽  
Danny N. Dhanasekaran
Keyword(s):  
High Throughput Sequencing ◽  
Critical Role ◽  
Therapy Resistance ◽  
Signaling Cascades ◽  
Clear Understanding ◽  
Sequencing Technologies ◽  
Cancer Cell Survival ◽  
Non Coding Rnas ◽  
Insight Into

Cancer is one of the leading causes of death worldwide. Multifactorial etiology of cancer and tumor heterogeneity are the two most acute challenges in existing diagnostic and therapeutic strategies for cancer. An effective precision cancer medicine strategy to overcome these challenges requires a clear understanding of the transcriptomic landscape of cancer cells. Recent innovative breakthroughs in high-throughput sequencing technologies have identified the oncogenic or tumor-suppressor role of several long non-coding RNAs (lncRNAs). LncRNAs have been characterized as regulating various signaling cascades which are involved in the pathobiology of cancer. They modulate cancer cell survival, proliferation, metabolism, invasive metastasis, stemness, and therapy-resistance through their interactions with specific sets of proteins, miRNAs and other non-coding RNAs, mRNAs, or DNAs in cells. By virtue of their ability to regulate multiple sets of genes and their cognate signaling pathways, lncRNAs are emerging as potential candidates for diagnostic, prognostic, and therapeutic targets. This review is focused on providing insight into the mechanisms by which different lncRNAs play a critical role in cancer growth, and their potential role in cancer diagnosis, prognosis, and therapy.

Regulation of Histone Deacetylases by MicroRNAs in Bone

2019 ◽  
Vol 20 (4) ◽  
pp. 356-367 ◽  
Author(s):  
S. Shreya ◽  
D. Malavika ◽  
V. Raj Priya ◽  
N. Selvamurugan
Keyword(s):  
Histone Deacetylases ◽  
Osteoblast Differentiation ◽  
Essential Role ◽  
Class Ii ◽  
Signaling Cascades ◽  
Transcriptional Level ◽  
Class Iii ◽  
Regulatory Factors ◽  
Non Coding Rnas ◽  
Class Iv

Formation of new bone by osteoblasts is mediated via the activation of signaling pathways, such as TGF-β, BMP, and Wnt. A number of transcription factors participate in the signaling cascades that are tightly regulated by other regulatory factors. Histone deacetylases (HDACs) are one such class of regulatory factors that play an essential role in influencing chromatin architecture and regulate the expression of the genes that play a role in osteoblast differentiation by the mechanism of deacetylation. Four classes of HDACs have been identified namely, class I, class II A, class II B, class III and class IV. MicroRNAs (miRNAs) are small fragments of non-coding RNAs typically 19-25 nucleotides long that target mRNAs to upregulate or downregulate gene expression at a post-transcriptional level. A number of miRNAs that target HDACs in bone have been recently reported. Hence, in this review, we elaborate on the various miRNAs that target the different classes of HDACs and impact of the same on osteogenesis.

Non-coding RNA Associated Competitive Endogenous RNA Regulatory Network: Novel Therapeutic Approach in Liver Fibrosis

2019 ◽  
Vol 19 (5) ◽  
pp. 305-317 ◽  
Author(s):  
Farooq Riaz ◽  
Dongmin Li
Keyword(s):  
Liver Fibrosis ◽  
Target Genes ◽  
Signaling Cascades ◽  
Circular Rnas ◽  
Pathological Feature ◽  
Non Coding Rna ◽  
Overwhelming Evidence ◽  
Competing Endogenous Rnas ◽  
Non Coding Rnas ◽  
Competitive Endogenous Rna

Liver fibrosis or scarring is the most common pathological feature caused by chronic liver injury, and is widely considered one of the primary causes of morbidity and mortality. It is primarily characterised by hepatic stellate cells (HSC) activation and excessive extracellular matrix (ECM) protein deposition. Overwhelming evidence suggests that the dysregulation of several noncoding RNAs (ncRNAs), mainly long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) contributes to the activation of HSC and progression of liver fibrosis. These ncRNAs not only bind to their target genes for the development and regression of liver fibrosis but also act as competing endogenous RNAs (ceRNAs) by sponging with miRNAs to form signaling cascades. Among these signaling cascades, lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA are critical modulators for the initiation, progression, and regression of liver fibrosis. Thus, targeting these interacting ncRNA cascades can serve as a novel and potential therapeutic target for inhibition of HSC activation and prevention and regression of liver fibrosis.

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