An integrated approach to understand the regulatory role of miR-27 family in breast cancer metastasis.

One of the prime reasons of increasing breast cancer mortality is metastasizing cancer cells. Owing to the side effects of clinically available drugs to treat breast cancer metastasis, it is of utmost importance to understand the underlying biogenesis of breast cancer tumorigenesis. In-silico identification of potential RNAs might help in utilizing the miR-27 family as a therapeutic target in breast cancer. The experimentally verified common interacting mRNAs for miR27 family are retrieved from three publicly available databases- TargetScan, miRDB and miRTarBase. Finally on comparing the common genes with HCMDB and GEPIA data, four breast cancer-associated differentially expressed metastatic mRNAs (GATA3, ENAH, ITGA2 and SEMA4D) are obtained. Corresponding to the miR27 family and associated mRNAs, interacting drugs are retrieved from Sm2mir and CTDbase, respectively. The interaction network-based approach was utilized to obtain the hub RNAs and triad modules by employing the 'Cytohubba' and 'MClique' plugins, respectively in Cytoscape. Further, sample-, subclass- and promoter methylation-based expression analyses reveals GATA3 and ENAH to be the most significant mRNAs in breast cancer metastasis having >10% genetic alteration in both METABRIC Vs TCGA datasets as per their oncoprint analysis via cBioPortal. Additionally, survival analysis in Oncolnc reveals SEMA4D as survival biomarker. Interactions among the miR27 family, their target mRNAs and drugs interacting with miRNAs and mRNAs can be extensively explored in both in-vivo and in-vitro setups to assess their therapeutic potential in the diminution of breast cancer.

Multi-OMICS approaches in cancer biology: New era in cancer therapy.

Innovative multi-omics frameworks integrate diverse datasets from the same patients to enhance our understanding of the molecular and clinical aspects of cancers. Advanced omics and multi-view clustering algorithms present unprecedented opportunities for classifying cancers into subtypes, refining survival predictions and treatment outcomes, and unravelling key pathophysiological processes across various molecular layers. However, with the increasing availability of cost-effective high-throughput technologies (HTT) that generate vast amounts of data, analyzing single layers often falls short of establishing causal relations. Integrating multi-omics data spanning genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes offers unique prospects to comprehend the underlying biology of complex diseases like cancer. This discussion explores algorithmic frameworks designed to uncover cancer subtypes, disease mechanisms, and methods for identifying pivotal genomic alterations. It also underscores the significance of multi-omics in tumor classifications, diagnostics, and prognostications. Despite its unparalleled advantages, the integration of multi-omics data has been slow to find its way into everyday clinics. A major hurdle is the uneven maturity of different omics approaches and the widening gap between the generation of large datasets and the capacity to process this data. Initiatives promoting the standardization of sample processing and analytical pipelines, as well as multidisciplinary training for experts in data analysis and interpretation, are crucial for translating theoretical findings into practical applications.

Human Pluripotent Stem Cell-Based Assays to Predict Developmental Toxicity.

Human beings are continuously exposed to various toxic substances throughout their lives, which affect their reproductive health and eventually the offspring they give birth to. Mainly, these toxins damage the heart and neurological development of the newborn, but most recently, they have begun to affect the musculoskeletal system as well. These toxins are usually present in food, pharmaceuticals, cosmetics, or even the polluted air that people breathe; as a result, the prevalence of birth defects is steadily rising. For this reason, it becomes a necessity to deploy a new set of assays to test for such toxins in industries to decrease the occurrence of developmental toxicity. These assays are exceedingly expensive when carried out conventionally using animal models or cells from such sources and have a lower predictive value due to the vast variation between animals and humans. To overcome such major problems, human pluripotent stem cells are now frequently used for these assays. These cells are easily available, are quickly generated from somatic cells (induce pluripotent stem cells), can be of human origin without harming people, and eliminate animal harm, which makes them the top choice of scientists for carrying out any in vitro developmental toxicity assays.This chapter, therefore, provides an overview of several steps that can be used to predict a compound's developmental toxicity by utilizing human pluripotent stem cells. Here, the easiest and most effective procedure has been outlined that can screen many compounds simultaneously.

Molecular targets and therapeutic strategies for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is known for its heterogeneous complexity and is often difficult to treat. TNBC lacks the expression of major hormonal receptors like estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 and is further subdivided into androgen receptor (AR) positive and AR negative. In contrast, AR negative is also known as quadruple-negative breast cancer (QNBC). Compared to AR-positive TNBC, QNBC has a great scarcity of prognostic biomarkers and therapeutic targets. QNBC shows excessive cellular growth and proliferation of tumor cells due to increased expression of growth factors like EGF and various surface proteins. This study briefly reviews the limited data available as protein biomarkers that can be used as molecular targets in treating TNBC as well as QNBC. Targeted therapy and immune checkpoint inhibitors have recently changed cancer treatment. Many studies in medicinal chemistry continue to focus on the synthesis of novel compounds to discover new antiproliferative medicines capable of treating TNBC despite the abundance of treatments currently on the market. Drug repurposing is one of the therapeutic methods for TNBC that has been examined. Moreover, some additional micronutrients, nutraceuticals, and functional foods may be able to lower cancer risk or slow the spread of malignant diseases that have already been diagnosed with cancer. Finally, nanomedicines, or applications of nanotechnology in medicine, introduce nanoparticles with variable chemistry and architecture for the treatment of cancer. This review emphasizes the most recent research on nutraceuticals, medication repositioning, and novel therapeutic strategies for the treatment of TNBC.

Understanding crosstalk of organ tropism, tumor microenvironment and noncoding RNAs in breast cancer metastasis.

Cancer metastasis is one of the major clinical challenges worldwide due to limited existing effective treatments. Metastasis roots from the host organ of origin and gradually migrates to different regional and distant organs. In different breast cancer subtypes, different organs like bones, liver, lungs and brain are targeted by the metastatic tumor cells. Cancer renders mortality to their respective metastasizing sites like bones, brain, liver, and lungs. Metastatic breast cancers are best treated and managed if detected at an early stage. Metastasis is regulated by various molecular activators and suppressors. The conventional theory of 'seed and soil' states that metastatic tumor cells move to tumor microenvironment that has favorable conditions like blood flow for them to grow just like seeds grows when planted in fertile land. Additionally, different coding as well as non-coding RNAs play a very significant role in the process of metastasis by modulating their expression levels leading to a crosstalk of various tumorigenic cascades. Treatments for metastasis is also very critical in controlling this lethal process. Detecting breast cancer metastasis at an early stage is crucial for managing and predicting metastatic progression. In this review, we have compiled several factors that can be targeted to manage the onset and gradual stages of breast cancer metastasis.

Unveiling the mechanistic role of the Aryl hydrocarbon receptor in environmentally induced Breast cancer.

The aryl hydrocarbon receptor (AhR) is a crucial cytosolic evolutionary conserved ligand-activated transcription factor and a pleiotropic signal transducer. The biosensor activity of the AhR is attributed to the promiscuity of its ligand-binding domain. Evidence suggests exposure to environmental toxins such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls and halogenated aromatic hydrocarbons activates the AhR signaling pathway. The constitutive activation of the receptor signaling system leads to multiple health adversities and enhances the risk of several cancers, including breast cancer (BC). This review evaluates several mechanisms that integrate the tumor-inducing property of such environmental contaminants with the AhR pathway assisting in BC tumorigenesis, progress and metastasis. Intriguingly, immune evasion is identified as a prominent hallmark in BC. Several emerging pieces of evidence have identified AhR as a potent immunosuppressive effector in several cancers. Through AhR signaling pathways, some tumors can avoid immune detection. Thus the relevance of AhR in the immunomodulation of breast tumors and its putative mode of action in the breast tumor microenvironment are discussed in this review. Additionally, the work also explores BC stemness and its associated inflammation in response to several environmental cues. The review elucidates the context-dependent ambiguous behavior of AhR either as an oncogene or a tumor suppressor with respect to its ligand. Conclusively, this holistic piece of literature attempts to potentiate AhR as a promising pharmacological target in BC and updates on the therapeutic manipulation of its various exogenous and endogenous ligands.

Multidimensional computational study to understand non-coding RNA interactions in breast cancer metastasis.

Metastasis is a major breast cancer hallmark due to which tumor cells tend to relocate to regional or distant organs from their organ of origin. This study is aimed to decipher the interaction among 113 differentially expressed genes, interacting non-coding RNAs and drugs (614 miRNAs, 220 lncRNAs and 3241 interacting drugs) associated with metastasis in breast cancer. For an extensive understanding of genetic interactions in the diseased state, a backbone gene co-expression network was constructed. Further, the mRNA-miRNA-lncRNA-drug interaction network was constructed to identify the top hub RNAs, significant cliques and topological parameters associated with differentially expressed genes. Then, the mRNAs from the top two subnetworks constructed are considered for transcription factor (TF) analysis. 39 interacting miRNAs and 1641 corresponding TFs for the eight mRNAs from the subnetworks are also utilized to construct an mRNA-miRNA-TF interaction network. TF analysis revealed two TFs (EST1 and SP1) from the cliques to be significant. TCGA expression analysis of miRNAs and lncRNAs as well as subclass-based and promoter methylation-based expression, oncoprint and survival analysis of the mRNAs are also done. Finally, functional enrichment of mRNAs is also performed. Significant cliques identified in the study can be utilized for identification of newer therapeutic interventions for breast cancer. This work will also help to gain a deeper insight into the complicated molecular intricacies to reveal the potential biomarkers involved with breast cancer progression in future.

Evaluating chemotherapeutic potential of soya-isoflavonoids against high penetrance genes in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer (BC) associated with a poor prognosis. Owing to the structural similarity with 17-ß-estradiol, consumption of soya-isoflavonoids are associated with a reduced rate of hormone-receptive BC incidence, but their role in TNBC is not deciphered in detail. This present study thus aims to investigate the therapeutic binding dynamics of dietary soya-flavonoids with the six high penetrance (HP) receptors in TNBC, viz. BRCA1, BRCA2, PALB2, PTEN, STK11 and TP53. Out of the 14 soya-flavonoids screened based on ADMET descriptors and several other physicochemical, bioavailability, drug and lead-likeness properties, four hits were shortlisted (Daidzein, Genistein, Glycitein and Biochanin A). Docking and molecular dynamics (MD) simulation revealed Genistein as the most potential multi-target inhibitor of the six TNBC HP genes. Additionally, Genistein exhibited excellent binding specificity with PTEN, a potent mediator of the PI3K signaling pathway in TNBC. The binding interaction of PTEN and Genistein was further compared against a standardized FDA-approved chemotherapeutic inhibitor, Olaparib, computed through various MD trajectory analysis, principal component analysis and computation of free energy landscape. This study reveals a comparatively better binding dynamics of PTEN-Genistein than PTEN-Olaparib. With a significant global surge in biomarker-based precision therapeutics in oncology, the results of this exhaustive in-silico study thus encourage the prospect of validating PTEN as a druggable target of Genistein, a unique drug-receptor combination in the future.Communicated by Ramaswamy H. Sarma.

Identification of pseudobaptigenin as a novel polyphenol-based multi-target antagonist of different hormone receptors for breast cancer therapeutics.

Breast cancer (BC) is one of the most prevalent cancers in the world and is one of the major reasons for the death of women worldwide. BC is majorly categorized based on the presence or absence of three cell receptors ER, PR and HER2. The latest treatment for BC involves interfering with the production and action of hormones such as estrogen and progesterone. These hormones bind with receptors such as ER and PR and enhance the growth and proliferation of the BC cells. Although the available are effective, the increasing resistance and side effects related to hormonal imbalance are significant and hence there is a need for designing. On the other hand, plant-derivative products have gained a lot of popularity for their promising anti-cancerous activities. Polyphenols are one such group of plant derivatives that have proven to be useful against cancer. In the present study, an in-silico approach was used to search for a polyphenol that can inhibit ER. In this work, a total of 750 polyphenols were taken into consideration. This number was narrowed down to 55, based on their ADMET properties. These 55 polyphenols were then docked to the receptors, ER, PR and HER2. The molecular docking was followed by Molecular Dynamics (MD) simulations. Based on molecular docking and MD simulation results it was concluded that Pseudobaptigenin has the potential to be an inhibitor of ER, PR and HER2.Communicated by Ramaswamy H. Sarma.

Docking and Molecular Dynamics Simulation Revealed the Potential Inhibitory Activity of Amygdalin in Triple-Negative Breast Cancer Therapeutics Targeting the BRCT Domain of BARD1 Receptor.

Triple-negative breast cancer (TNBC), is diagnosed as the most lethal molecular subtype of breast cancer (BC) preceded by an extremely poor prognosis. For enabling effective TNBC therapy, the identification of novel druggable biomarkers is an earnest need. Multigene paneling and genomewide association studies identify multiple genes with high-to-moderate penetrance in TNBC. Modern computer-aided drug designing techniques, thus aim to design more cost-effective natural small molecule inhibitors for TNBC prevention and diagnosis. Here Amygdalin, a natural glycosidic inhibitor is docked and simulated against three such high-to-moderate penetrance genes identified in TNBC, BARD1, RAD51, and PALB2. The preliminary result of the analysis, reports a highest, intermediate, and least binding energy score of - 6.69 kcal/mol, - 5.09 kcal/mol, and - 4.89 kcal/mol in BARD1, RAD51, and PALB2, respectively. The best-docked protein-ligand complex (BARD1-Amygdalin) was then simulated and compared with an approved drug for TNBC treatment, Olaparib. A comparable binding energy score of - 8.53 kcal/mol was obtained by docking olaparib with BARD1. A 100 ns MD simulation revealed, Amygdalin forms more H-bonds, providing more stable and compact protein-ligand complex with BARD1 than compared to Olaparib. The result was also supported by calculation of solvent accessible surface area and analysis of radius of gyration. Thus, our findings suggest that role of Amygdalin can further be studied in details for TNBC therapeutics, which was found to target the BRCT domain of the BARD1 receptor in stable manner. Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary. Name and affiliations are correctly identified.

Cancer secretome: finding out hidden messages in extracellular secretions.

Secretome analysis has gained popularity recently as a very well-designed proteomic approach that is being used to study various interactions and their effects on cellular activity. This analysis is especially helpful while studying the effects of the cells on their microenvironment, paracrine and autocrine processes, their therapeutic purposes, and as a new diagnostic perspective. Cancer is a condition rather than a specific type of disease and is still yet to be fully understood. Cancer secretome is a fairly new concept that is being implemented to examine the interactions taking place in the tumor microenvironment and can help to understand the phenomena like induction of tumorigenesis, stimulation of immune cells, etc. The secretome analysis helps to gain a different perspective on the existing knowledge on cancer and its effects. The recent advances in secretome studies are directed toward secreted components as drug targets, biomarkers, and companion tools for diagnostic and prognostic purposes in cancer. This review aims to find the interactors in different types of cancer and understand the existing unstructured secretome data and its application in prognosis, diagnosis, and in biomarker study.

Recent Advances and Therapeutic Strategies Using CRISPR Genome Editing Technique for the Treatment of Cancer.

CRISPR genome editing technique has the potential to target cancer cells in a precise manner. The latest advancements have helped to address one of the prominent concerns about this strategy which is the off-target integrations observed with dsDNA and have resulted in more studies being carried out for potentially safer and more targeted gene therapy, so as to make it available for the clinical trials in order to effectively treat cancer. CRISPR screens offer great potential for the high throughput investigation of the gene functionality in various tumors. It extends its capability to identify the tumor growth essential genes, therapeutic resistant genes, and immunotherapeutic responses. CRISPR screens are mostly performed in in vitro models, but latest advancements focus on developing in vivo models to view cancer progression in animal models. It also allows the detection of factors responsible for tumorigenesis. In CRISPR screens key parameters are optimized in order to meet proficient gene targeting efficiencies. It also detects various molecular effectors required for gene regulation in different cancers, essential pathways which modulate cytotoxicity to immunotherapy in cancer cells, important genes which contribute to cancer cell survival in hypoxic states and modulate cancer long non-coding RNAs. The current review focuses on the recent developments in the therapeutic application of CRISPR technology for cancer therapy. Furthermore, the associated challenges and safety concerns along with the various strategies that can be implemented to overcome these drawbacks has been discussed.

A novel probiotic strain of Lactobacillus fermentum TIU19 isolated from Haria beer showing both in vitro antibacterial and antibiofilm properties upon two multi resistant uro-pathogen strains.

Probiotics with antimicrobial activity are gaining interest as a topic in the research field. Urinary tract infections (UTIs), acquired in the hospital or the community, are among the most prevalent infections. The emergence of multidrug resistance (MDR) uro-pathogens has made the current situation more critical in terms of global public health. To face this situation, in this study, Lactobacillus fermentum TIU19 (L. fermentum TIU19) was isolated and characterized as a new probiotic strain of the rice-based fermented beverage Haria. Subsequently, we also investigated its application as a biological agent that inhibits the growth of multidrug-resistant uro-pathogens, Escherichia coli, and Enterococcus faecalis. The results showed that, the isolated strain L. fermentum TIU19 was sensitive to all antibiotics tested except vancomycin and was devoid of virulence factors, such as haemolytic and gelatinase activities. Therefore, it may be considered safe for public health. It has many probiotic properties, such as survival in simulated gastrointestinal fluid, antioxidant activity, ß-galactosidase producing ability, high cell surface hydrophobicity, adhesion ability to epithelial cells, and strong biofilm producer. The growth inhibitory and antibiofilm activities were shown against two uro-pathogens. All these results suggest that L. fermentum TIU19 can be explored as a potential probiotic with antagonistic activity against MDR uro-pathogenic E. coli and E. faecalis.

An integrated approach to understand fluid shear stress-driven and reactive oxygen species-mediated metastasis of colon adenocarcinoma through mRNA-miRNA-lncRNA-circRNA networks.

Development of colon adenocarcinoma (COAD) metastasis involves several mediators including fluid shear stress (FSS), intracellular ROS levels, and non-coding RNAs. In our present study, we identified and investigated the role of regulatory non-coding RNA molecules specifically involved in COAD metastasis and their association with FSS and ROS. Interactions between the mRNAs associated with FSS and ROS, the corresponding microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in COAD metastasis were used to generate the mRNA-miRNA-lncRNA-circRNA network. Experimental validation of the identified RNA hubs using quantitative real-time PCR demonstrated a direct effect of the FSS on their expression levels in cancer cells. FSS resulted in the downregulation of HMGA1 and RAN, as well as the upregulation of HSP90AA1, PMAIP1 and BIRC5. Application of shear stress also led to downregulation of hsa-miR-26b-5p and hsa-miR-34a-5p levels in HCT116 cells. Further, functional enrichment and survival analysis of the significant miRNAs, as well as the OncoPrint and the survival analyses of the selected mRNAs were performed. Subsequently, their functional role was also corroborated with existing literature. Ten significant miRNA hubs were identified, out of which hsa-miR-17-5p and hsa-miR-20a-5p were found to interact with lncRNA (CCAT2) while hsa-miR-335 was found to interact with four circRNAs. Fifteen significant miRNAs were identified in 10 different modules suggesting their importance in FSS and ROS-mediated COAD metastasis. Finally, 10 miRNAs and 3 mRNAs associated with FSS and/or ROS were identified as significant overall survival markers; 33 mRNAs were also identified as metastasis-free survival markers whereas 15 mRNAs showed > 10% gene alterations in TCGA-COAD data and may serve as promising therapeutic biomarkers in the COAD metastasis.

An overview of synthesis, characterization, applications and associated adverse effects of bioactive nanoparticles.

A particle with a diameter ranging from 1 to 100 nm is considered a nanoparticle (NP). Owing to their small size and high surface area, NPs possess unique physical, chemical and biological properties as compared to their bulkier counterparts. This paper describes various physico-chemical as well as green methods that can be used to synthesize different types of NPs including carbon-based, ceramic, metal, semiconductor, polymeric and lipid-based NPs. These methods can be categorized into either top-down or bottom-up approaches. Electron microscopy, atomic force microscopy, dynamic light scattering, X-ray diffraction, zeta-potential instrument, liquid chromatography-mass spectrometry, fourier transform infrared spectroscopy and thermogravimetric analysis are the techniques discussed in the characterization of NPs. This review provides an insight into the extraordinary properties of NPs that have opened the doors for endless biomedical applications like drug delivery, photo-ablation therapy, biosensors, bio-imaging and hyperthermia. In addition, NPs are also involved in improving crop growth, making protective clothing, cosmetics and energy reserves. This review also specifies adverse health effects associated with NPs such as hepatotoxicity, genotoxicity, neurotoxicity, etc., and inhibitory effects on plant growth and aquatic life. Further, in-vitro toxicity assessment assays for cell proliferation, apoptosis, necrosis and oxidative stress, as well as in-vivo toxicity assessment like biodistribution, clearance, hematological, serological and histological studies, are discussed here. Lastly, the authors have mentioned various measures that can be adopted to minimize the toxicity associated with NPs such as green synthesis, use of stabilizers, gene gun, polymer shell, microneedle capsule, etc.

Tetracycline-loaded magnesium oxide nanoparticles with a potential bactericidal action against multidrug-resistant bacteria: In vitro and in vivo evidence.

Worldwide, the emergence of diarrhoea-causing multi-drug resistant (MDR) bacteria has become a crucial problem in everyday life. Tetracycline (TC) is a bacteriostatic agent that has a wide spectrum of antibacterial activity. One potential strategy to enhance the penetration and antibacterial activity of antibiotics is the use of nanotechnology. In this context, this study dealt with the synthesis of TC loading in biocompatible magnesium oxide nanoparticles (MgONPs), its characterization, and the potency of killing against diarrhoea-causing MDR bacteria E. coli and S. flexneri. TC loaded- MgONPs (MgONPs-TC) were characterized by DLS, SEM-EDS, UV-vis spectroscopy, and FTIR techniques with adequate physical properties. Antibacterial and antibiofilm studies indicate that this nanoparticle successfully eradicated both planktonic and sessile forms of those bacteria. It also significantly reduced the production of bacterial EPS, different levels of antioxidant enzymes, and induced reactive oxygen species (ROS) in the bacterial cell as a mode of antibacterial action. In particular, MgONPs-TC were efficient in reducing the colonization of MDR E. coli and S. flexneri in the C. elegans model. Therefore, all these data suggest that MgONPs-TC are a highly promising approach to combating diseases associated with diarrhoea-causing MDR bacteria in the medical field with limited health care budgets.

Non-coding RNAs associated with autophagy and their regulatory role in cancer therapeutics.

Cancer widely affects the world's health population and ranks second leading cause of death globally. Because of poor prognosis of various types of cancer such as sarcoma, lymphoma, adenomas etc., their high recurrence and metastasis rate and low early diagnosis rate have become concern lately. Role of autophagy in cancer progression is being studied since long. Autophagy is cell's self-degradative mechanism towards stress and has role in degradation of the cytoplasmic macromolecules which has potential to damage other cytosolic molecules. Autophagy can promote as well as inhibit tumorigenesis depending upon the associated protein combinations in cancer cells. Recent studies have shown that non-coding RNAs (ncRNAs) do not code for protein but play essential role in modulation of gene expression. At transcriptional level, different ncRNAs like lncRNAs, miRNAs and circRNAs directly or indirectly affect different stages of autophagy like autophagy-dependent and non-apoptotic cell death in cancer cells. This review focuses on the involvement of ncRNAs in autophagy and the modulation of several cancer signal transduction pathways in cancers such as lung, breast, prostate, pancreatic, thyroid, and kidney cancer.

Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer.

Prostate cancer (PCa) is one of the most frequently occurring cancers among men, and the current statistics show that it is the second leading cause of cancer-related deaths among men. Over the years, research in PCa treatment and therapies has made many advances. Despite these efforts, the standardized therapies such as radiation, chemotherapy, hormonal therapy and surgery are not considered completely effective in treating advanced and metastatic PCa. In most situations, fast-dividing tumor cells are targeted, leaving behind relatively slowly dividing, chemoresistant cells known as cancer stem cells. Therefore, following the seemingly successful treatments, the lingering quiescent cancer stem cells are able to renew themselves, undergo differentiation into mature tumor cells, and sufficiently reinitiate the disease, leading to cancer relapse. Thus, prostate cancer stem cells (PCSCs) have been reported to play a vital role in controlling the dynamics of tumorigenesis, progression, and resistance to therapies in PCa. However, the complete knowledge on the mechanisms regulating the stemness of PCSCs is still unclear. Thus, studying the stemness of PCSCs will allow for the development of more effective cancer therapies due to the durable response, resulting in a reduction in recurrences of cancer. In this Review, we will specifically describe the molecular mechanisms responsible for regulating the stemness of PCSCs. Furthermore, current developments in stem cell-specific therapeutic approaches along with future prospects will also be discussed.

The functional significance and cross-talk of non-coding RNAs in triple negative and quadruple negative breast cancer.

One of the leading causes of cancer-related deaths worldwide is breast cancer, among which triple-negative breast cancer (TNBC) is the most malignant and lethal subtype. This cancer accounts for 10-20% of all breast cancer deaths. Proliferation, tumorigenesis, and prognosis of TNBC are affected when the androgen receptor (AR) is not expressed, and it is classified as quadruple negative breast cancer (QNBC). Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play a significant role in tumorigenesis by virtue of their oncogenic and tumor-suppressive properties. To regulate tumorigenesis, miRNAs interact with their target mRNAs and modulate their expression, whereas lncRNAs can either act alone or interact with miRNAs or other molecules through various signaling pathways. Conversely, circRNAs regulate tumorigenesis by acting as miRNA sponges predominantly. Recently, non-coding RNAs were studied comprehensively for their roles in tumor proliferation, progression, and metastasis. As a result of existing studies and research progress, non-coding RNAs have been implicated in TNBC, necessitating their use as biomarkers for future diagnostic applications. In this review, the non-coding RNAs are explicitly implicated in the regulation of breast cancer, and their cross-talk between TNBC and QNBC is also discussed.

Exploring clinical implications and role of non-coding RNAs in lung carcinogenesis.

Lung cancer is the utmost familiar category of cancer with greatest fatality rate worldwide and several regulatory mechanisms exercise cellular control on critical oncogenic trails implicated in lung associated carcinogenesis. The non-coding RNAs (ncRNAs) are shown to play a variety of regulatory roles, including stimulating cell proliferation, inhibiting programmed cell death, enhancing cancer cell metastatic ability and acquiring resistance to drugs. Furthermore, ncRNAs exhibit tissue-specific expression as well as great stability in bodily fluids. As a consequence, they are strong contenders for cancer based theragnostics. microRNA (miRNA) alters gene expression primarily by either degrading or interfering with the translation of targeted mRNA and long non-coding RNAs (lncRNAs) can influence gene expression by targeting transcriptional activators or repressors, RNA polymers and even DNA-duplex. lncRNAs are typically found to be dysregulated in lung cancer and hence targeting ncRNAs could be a viable strategy for developing potential therapies as well as for overcoming chemoresistance in lung cancer. The purpose of this review is to elucidate the role of ncRNAs, revisiting the recent studies in lung cancer.