Current Molecular Medicine - Volume 22, Issue 10, 2022

The mechanisms governing the development and progression of cancers are believed to be the consequence of hereditary deformities and epigenetic modifications. Accordingly, epigenetics has become an incredible and progressively explored field of research to discover better prevention and therapy for neoplasia, especially triple-negative breast cancer (TNBC). It represents 15-20% of all invasive breast cancers and will, in general, have bellicose histological highlights and poor clinical outcomes. In the early phases of triple-negative breast carcinogenesis, epigenetic deregulation modifies chromatin structure and influences the plasticity of cells. It up-keeps the oncogenic reprogramming of malignant progenitor cells with the acquisition of unrestrained selfrenewal capacities. Genomic impulsiveness in TNBC prompts mutations, copy number variations, as well as genetic rearrangements, while epigenetic remodeling includes an amendment by DNA methylation, histone modification, and noncoding RNAs of gene expression profiles. It is currently evident that epigenetic mechanisms assume a significant part in the pathogenesis, maintenance, and therapeutic resistance of TNBC. Although TNBC is a heterogeneous malaise that is perplexing to describe and treat, the ongoing explosion of genetic and epigenetic research will help to expand these endeavors. Latest developments in transcriptome analysis have reformed our understanding of human diseases, including TNBC at the molecular medicine level. It is appealing to envision transcriptomic biomarkers to comprehend tumor behavior more readily regarding its cellular microenvironment. Understanding these essential biomarkers and molecular changes will propel our capability to treat TNBC adequately. This review will depict the different aspects of epigenetics and the landscape of transcriptomics in triple-negative breast carcinogenesis and their impending application for diagnosis, prognosis, and treatment decision with the view of molecular medicine.

Colorectal cancer (CRC) is one of the main causes of malignancy-related mortality worldwide. It was well-identified that microRNAs (miRNAs) decisively participate in cellular biological pathways; in a way that their deregulated expression causes CRC progression. miRNAs can control the translation and degradation of mRNAs by binding to various molecular targets involved in different biological processes, including growth, apoptosis, cell cycle, autophagy, angiogenesis, metastasis, etc. The functions of these dysregulated miRNAs may be either oncogenic or tumorsuppressive. Therefore, these miRNAs can be contributed to prognostic, diagnostic, and therapeutic approaches in CRC. In this study, we reviewed the tumor-suppressive and oncogenic functions of miRNAs in CRC and assessed their molecular activities in CRC development. However, further investigation for the involvement of dysregulated miRNAs in CRC progression is required.

MicroRNAs (miRs) is a class of conserved, small, noncoding RNA molecules that modulate gene expression post-transcriptionally. miR-148b is a member of miR- 148/152 family generally known to be a tumor suppressor via its effect on different signaling pathways and regulatory genes. Aberrant expression of miR-148b has recently been shown to be responsible for tumorigenesis of several different cancer types. This review discusses the current evidence regarding the involvement of miR-148b expression in human cancers and its potential clinical importance for tumor diagnosis, prognosis, and therapeutics.

Metabolomics is an omics approach of systems biology that involves the development and assessment of large-scale, comprehensive biochemical analysis tools for metabolites in biological systems. This review describes the metabolomics workflow and provides an overview of current analytic tools used for the quantification of metabolic profiles. We explain analytic tools such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, ionization techniques, and approaches for data extraction and analysis.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are proficient in regulating gene expression post-transcriptionally. Considering the recent trend in exploiting non-coding RNAs (ncRNAs) as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agents against angiogenesis is an important scientific aspect. An estimated 70% of the genome is actively transcribed, only 2% of which codes for known protein-coding genes. Long noncoding RNAs (lncRNAs) are a large and diverse class of RNAs > 200 nucleotides in length, and not translated into protein, and are of utmost importance and it governs the expression of genes in a temporal, spatial, and cell context-dependent manner. Angiogenesis is an essential process for organ morphogenesis and growth during development, and it is relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro-and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases, including breast cancer. Signaling pathways involved here are tightly controlled systems that regulate the appropriate timing of gene expression required for the differentiation of cells down a particular lineage essential for proper tissue development. Lately, scientific reports are indicating that ncRNAs, such as miRNAs, and lncRNAs, play critical roles in angiogénesis-related to breast cancer. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signaling pathways regulated by these ncRNAs with molecular medicine perspective, are highlighted in this write-up.

The coronavirus disease 2019 (COVID-19) is a contagious disease that is caused by a novel coronavirus. The human coronavirus (HCoV) is recognized as one of the most rapidly evolving viruses owing to its high genomic nucleotide substitution rates and recombination. Among the severe acute respiratory syndrome (SARS) and Middle- East respiratory syndrome (MERS), COVID-19 has spread more rapidly and increased the level of globalization and adaptation of the virus in every environmental condition due to their high rate of molecular diversity. The whole article highlights the general characteristics of coronavirus, their molecular diversity, and molecular protein targeting against COVID-19 with their newer approaches. Through this review, an attempt has been made to critically evaluate the recent advances and future aspects that are helpful to the treatment of COVID-19 based on the present understanding of SARS-CoV-2 infections, which may offer new insights and potential therapeutic targets for the treatment of COVID-19.

Background: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-ΚB) signaling and attenuates the severity of some muscle diseases. Objective: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber´s diameter in a murine model of sarcopenia by aging. Methods: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber´s diameter were measured. Results: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber´s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber´s diameter. Conclusion: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber´s diameter are potentiated.

Background: Dezocine is an opioid analgesic that can affect the immune system. Here, we explored the synergy of high concentration of Dezocine and programmed death-ligand 1 (PD-L1) with regards to immune escape and glucose metabolism in lung cancer (LC). Methods: PD-L1 level in human LC cell lines was determined and the influence of Dezocine at different concentrations for the proliferation of LC cells was identified. Next, LC cells were transfected to alter PD-L1 level, and exposed to Dezocine at 8 μg/mL to explore their effects on cell proliferation, production of interferon-γ (IFN-γ), contents of glucose, lactate, and NADPH/NADP+, and activation of the nuclear factor-ΚB (NF-ΚB) pathway. Results: PD-L1 level was increased in LC cells and Dezocine (8 μg/mL) impaired the proliferation of LC cells. Down-regulating PD-L1 inhibited cell proliferation, enhanced production of IFN-γ, and reduced the contents of glucose, lactate, and NADPH/NADP+, while up-regulating PD-L1 caused the opposite results. Dezocine (8 μg/mL) induced immune escape and glucose metabolism in LC, and Dezocine-induced effects were reversed by down-regulating PD-L1. Dezocine (8 μg/mL) up-regulated PD-L1 by activating the NF-ΚB pathway. Conclusion: Dezocine at 8 μg/mL promotes immune escape and glucose metabolism in LC through up-regulating PD-L1 and activating the NF-ΚB pathway.

Background: The establishment of strategy to inhibit the virus replication is an attractive means in combating SARS-CoV-2 infection. Objective: We studied phyto-compounds from Strychnos nux-vomica (a poisonous plant) against SARS-CoV-2 RNA-dependent RNA polymerase by computational methods. Methods: Molecular docking, molecular dynamics (MD) simulation and energetics calculations were employed to elucidate the role of the phyto-compounds. Results: Ergotamine with a binding free energy of -14.39 kcal/mol showed a promising capability in terms of binding affinity and the interaction to conserved motifs, especially the SDD signature sequence. The calculated dissociation constants for ATP, ergotamine, isosungucine and sungucine were 12 μM, 0.072 nM, 0.011 nM and 0.152 nM, respectively. The exhibited kd by these phyto-compounds reflected tens of thousands fold potency as compared to ATP. The binding free energies of sungucine and isosungucine were much lower (-13.93 and -15.55 kcal/mol, respectively) compared to that of ATP (-6.98 kcal/mol). Conclusion: Sharing the same binding location as that of ATP and having high binding affinities, Ergotamine, Isosungucine, Sungucine and Strychnine N-oxide could be effective in controlling the SARS-CoV-2 virus replication by blocking the ATP and inhibiting the enzyme function.

Background: Expression levels of collagens have been implicated in the progression of various cancers and interaction with cytokeratins but are not well studied in bladder cancer (BC). Therefore, we analyzed the gene and protein expression levels of collagen 1A1 (Col1a1/COL1A1), collagen 3A1 (col3a1/COL3A1), collagen 5A2 (col5a2/COL5A2), cytokeratin 14 (krt14/CK14), and cytokeratin 17 (krt17/CK17) in urothelial BC samples of different stages. Methods: In total, 102 fresh frozen and 190 formalin-fixed and paraffin-embedded (FFPE) samples were tested using immunohistochemistry and RT-qPCR. Expression levels were correlated with clinicopathological and follow-up data. Results: Col1a1, col3a1, col5a2 and krt14 mRNA levels were significantly overexpressed in high-grade and muscle-invasive BC (MIBC) compared to low-grade and non-muscle invasive BC (NMIBC) cases. Disease-specific survival (DSS) was shorter in patients with high expression levels of col1a1 (p = 0.004), col3a1 (p = 0.004), and col5a2 (p = 0.028). CK14 (p = 0.020), COL3A1 (p = 0.006), and Col5A2 (p = 0.006) protein expression levels were significantly higher and protein expression levels of CK17 (p = 0.05) were significantly lower in MIBC compared to NMIBC. Furthermore, CK14 (p = 0.002) and COL5A2 (p = 0.006) protein expression level were significantly higher in high-grade compared to low-grade BC. DSS was shorter in patients with high expression levels of COL5A2 (p = 0.033) and CK14 (p = 0.042). Conclusion: Expression changes of collagens and cytokeratins are univariable prognostic markers in BC.