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The Multifaceted Role of Annexin A1 in Colorectal Cancer: From Molecular Mechanisms to Predictive and Prognostic Implications.

Annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein, is considered a key modulator of cancer biology. Numerous pieces of evidence support its multifaceted involvement in tumor progression, metastatic dissemination, immune escape, and resistance to therapy in various malignancies, such as melanoma, along with liver, lung, and digestive tract tumors, including stomach and colorectal cancer (CRC). Although colon and rectal cancer (RC) exhibit overlapping characteristics, they are classified as separate clinical entities due to differences in tumor biology and therapy approaches.

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… Ubiquitination and SUMOylation of annexin A1 and helicase activity Biochim. Biophys. Acta 2010 1800 899 905 10.1016/j.bbagen.2010.03.020 20359522 53. Moreli J.B. Santos M.R.D. Calderon I.M.P. Hebeda C.B. Farsky S.H.P. Bevilacqua E. Oliani S.M. …

Epigenetic mechanisms in cardiovascular complications of diabetes: towards future therapies.

The pathophysiological mechanisms of cardiovascular disease and microvascular complications in diabetes have been extensively studied, but effective methods of prevention and treatment are still lacking. In recent years, DNA methylation, histone modifications, and non-coding RNAs have arisen as possible mechanisms involved in the development, maintenance, and progression of micro- and macro-vascular complications of diabetes. Epigenetic changes have the characteristic of being heritable or deletable. For this reason, they are now being studied as a therapeutic target for the treatment of diabe

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… In addition, histones residues can undergo phosphorylation, ubiquitination, SUMOylation, glycosylation, citrullination and many other modifications have been discovered recently (Impivaara et al. 1986 ; Cavalieri 2021 ). …

JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies.

JAK/STAT signaling pathway is one of the important regulatory signaling cascades for the myriad of cellular processes initiated by various types of ligands such as growth factors, hormones, and cytokines. The physiological processes regulated by JAK/STAT signaling are immune regulation, cell proliferation, cell survival, apoptosis and hematopoiesis of myeloid and non-myeloid cells. Dysregulation of JAK/STAT signaling is reported in various immunological disorders, hematological and other solid malignancies through various oncogenic activation mutations in receptors, downstream mediators, and a

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable s

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as

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… There are numerous types of PTMs, including acetylation, methylation, phosphorylation, ubiquitination and sumoylation, each having its own role in gene regulation as well as in other mechanisms, like DNA repair, cell division and differentiation ( Burlibaș;a and Zărnescu, 2013 ; Gong and Miller, 2019 …

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

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… The addition of chemical groups to histone tails, including acetylation, methylation, phosphorylation, sumoylation, and ubiquitination, significantly affects the physical structure and transcriptional capacity of chromatin. …

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

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… These include acylation, which comprises acetylation, benzoylation, butyrylation, crotonylation, glutarylation, and lactylation, as well as modifications such as ADP-ribosylation, dopaminylation, glycosylation, methylation, phosphorylation, serotonylation, sumoylation, and ubiquitination [ 24 , 25 ]. …

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.

Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover

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… Abbreviation: Ac, acetylation; ADP-ribo, ADP ribosylation; CNV, copy number variation; Glyco, glycosylation; Lipid, lipidation; lncRNA, long non-coding RNA; Me, methylation; miRNA, microRNA; ncRNA, non-coding RNA; OH, oxidrylic group; P, phosphorylation; SNV, single nucleotide variants; S-S, disulphide; Sumo, Sumoylation …

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges.

Uncontrolled inflammation is a salient factor in multiple chronic inflammatory diseases and cancers. In this review, we provided an in-depth analysis of the relationships and distinctions between uncontrolled inflammation, fibrosis and cancers, while emphasizing the challenges and opportunities of developing novel therapies for the treatment and/or management of these diseases. We described how drug delivery systems, combination therapy and the integration of tissue-targeted and/or pathways selective strategies could overcome the challenges of current agents for managing and/or treating chroni

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… SUMOylation of ROR-γt inhibits IL-17 expression and inflammation via HDAC2. Nat. Commun. 2018;9:1–11. doi: 10.1038/s41467-018-06924-5. 19. Ranneh Y., Ali F., Akim A.M., Hamid H.A., Khazaai H., Fadel A. …

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthet

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… Multiple post-translational modifications of tubulin, such as phosphorylation, acetylation, methylation, polyamination, palmitoylation, ubiquitination, glycosylation, arginylation, sumoylation, succination, and O-Glc-NAcylation also contribute to its diversity and microtubule biology. …

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

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… typically characterized by the presence of protein aggregates in the cytoplasm of motor neurons; the TAR DNA-binding protein (TDP43) is the main component of these pathological deposits. 178 A wide range of posttranslational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, sumoylation …

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A m

RNA метилтрансферазы METTL8 устанавливает m3C32 в митохондриальном tRNASThr/Ser (UCN) для оптимизации структуры trNA и митохондриального перевода.

Модифицированные нуклеотиды в tRNA являются важными определяющими факторами сворачивания, структуры и функции. Здесь мы идентифицируем METTL8 как митохондриальный белок и активный РНК метилтрансферазы, ответственный за установку m3C32 в митохондриале человека (mt-)tRNAThr и mt-tRNAser (UCN). METTL8 имеет перекрестные связи с антикодоновой стволовой петлей (ASL) многих мт-тРНК в клетках, в связи с чем возникает вопрос о том, каким образом достигается целевая специфичность метилирования. Расчленение элементов распознавания mt-tRNA выявило наличие U34G35 и t6A37/(ms2)i6A37, которые одновременно п

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

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… PTMs encompass a wide range of chemical reactions, including ubiquitination, SUMOylation, GlcNAcylation, phosphorylation, methylation, and acetylation [ 9 , 10 ]. …

Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to

Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.

Pancreatic neuroendocrine tumors (PNETs) are characterized by dysregulated signaling pathways that are crucial for tumor formation and progression. The efficacy of traditional therapies is limited, particularly in the treatment of PNETs at an advanced stage. Epigenetic alterations profoundly impact the activity of signaling pathways in cancer development, offering potential opportunities for drug development. There is currently a lack of extensive research on epigenetic regulation in PNETs. To fill this gap, we first summarize major signaling events that are involved in PNET development. Then,

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… This is by no means all-encompassing, as we recognized that we would not discuss other epigenetic modifications, including RNA methylation, histone ubiquitylation, phosphorylation, SUMOylation, ADP ribosylation, citrullination, and biotinylation at specific amino acid residues [ 25 ]. 2. …

Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential.

Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increa

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… These changes encompass DNA and RNA modifications by methylation and long and short noncoding RNAs, while histone and other proteins can be post-translationally modified via processes such as acetylation, phosphorylation, methylation, SUMOylation, ubiquitination or poly(ADP-ribosyl)ation (PARylation) …

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.

Colorectal cancer (CRC) represents the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The modern concept of cancer biology indicates that cancer is formed of a small population of cells called cancer stem cells (CSCs), which present both pluripotency and self-renewal properties. These cells are considered responsible for the progression of the disease, recurrence and tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, and self-renewal properties, and most of them are dysregulated in CSCs, includ

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… Although the loss of heterozygosity on chromosome 18 may be the main cause of Smad4 loss in CRC, there are other post‐transcriptional and post‐translational mechanisms that can contribute to its loss or dysfunction, such as ubiquitylation, sumoylation, and microRNA interference [ 240 ]. …

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… Antiviral IFN-I signaling is also regulated by covalent protein modification via ligation of small ubiquitin-like modifier (sumoylation) [ 32 ]. …

Anticancer Role of PPARgamma Agonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes.

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-gamma agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARgamma agonists in the treatment and prevention of