Exosomes multiplex profiling, a promising strategy for early diagnosis of laryngeal cancer.

BACKGROUND: Exosomes are nanosized vesicles released from all cells into surrounding biofluids, including cancer cells, and represent a very promising direction in terms of minimally invasive approaches to early disease detection. They carry tumor-specific biological contents such as DNA, RNA, proteins, lipids, and sugars, as well as surface molecules that are able to pinpoint the cellular source. By the above criteria, exosomes may be stratified according to the presence of tissue and disease-specific signatures and, due to their stability in such biofluids as plasma and serum, they represent an indispensable source of vital clinical insights from liquid biopsies, even at the earliest stages of cancer. Therefore, our work aimed to isolate and characterize LCa patients' derived exosomes from serum by Flow Cytometry in order to define a specific epitope signature exploitable for early diagnosis. METHODS: Circulating exosomes were collected from serum collected from 30 LCa patients and 20 healthy volunteers by the use of antibody affinity method exploiting CD63 specific surface marker. Membrane epitopes were then characterized by Flow cytometry multiplex analysis and compared between LCa Patients and Healthy donors. Clinical data were also matched to obtain statistical correlation. RESULTS: A distinct overexpression of CD1c, CD2, CD3, CD4, CD11c, CD14, CD20, CD44, CD56, CD105, CD146, and CD209 was identified in LCa patients compared to healthy controls, correlating positively with tumor presence. Conversely, CD24, CD31, and CD40, though not overexpressed in tumor samples, showed a significant correlation with nodal involvement in LCa patients (p < 0.01). CONCLUSION: This approach could allow us to set up a cost-effective and less invasive liquid biopsy protocol from a simple blood collection in order to early diagnose LCa and improve patients' outcomes and quality of life.

Tissue expression of miR-449a as risk factor for occult neck metastasis in patients with cT3-T4 N0 laryngeal cancer. A pilot study.

OBJECTIVE: To explore the potential role of miR-449a as biomarker for laryngeal squamous cell carcinoma (LSCC), especially in the decision strategy of neck dissection (ND). METHODS: Each patient underwent total laryngectomy and bilateral ND (levels II-IV); during surgery, tissue samples of around 1 × 0.5 cm were extracted from both healthy tissue adjacent to the tumor and the visibly affected tumor tissue. The extraction of total RNA, encompassing miRNA, was performed using a mirVana PARIS kit. To detect miR449a, cDNA was synthesized from 200 ng of RNA using a TaqMan miRNA reverse transcription kit. RESULTS: The study group was formed of 66 patients (62 males, and 4 females) with LSCC, aged between 39 and 77 years (mean 60 + 14.56 yr). MiR-449a was up-regulated in twenty-eight tumors (42%), while it was down-regulated in 38 samples (58%). In the present study, there was a statistical relevance for miR-449a tissue expression for pN staging (p = 0.017), and PNI (p = 0.005). Eight tumors (12%) cN0 became pN + showing occult cervical lymph node metastases at the final histopathological examination, and all of these patients showed miR-449a downregulation. CONCLUSION: Super-selective ND (sparing the sub evels IIb and IV) might be the approach to cT3-T4 N0 LSCCs with upregulation of miR-449a; on the other hand, to ensure and effective control of occult neck metastases it would be appropriate to reserve elective ND (including sublevels IIb and IV) for cT3-T4 N0 LSCCs with miR-449a downregulation. Although promising, due to the small size of the cohort, the results of this work can be considered preliminary and need to be confirmed by prospective and larger studies.

microRNA Detection via Nanostructured Biochips for Early Cancer Diagnostics.

MicroRNA (miRNA) are constituted of approximately 22 nucleotides and play an important role in the regulation of many physiological functions and diseases. In the last 10 years, an increasing interest has been recorded in studying the expression profile of miRNAs in cancer. Real time-quantitative polymerase chain reaction (RT-qPCR), microarrays, and small RNA sequencing represent the gold standard techniques used in the last 30 years as detection methods. The advent of nanotechnology has allowed the fabrication of nanostructured biosensors which are widely exploited in the diagnostic field. Nanostructured biosensors offer many advantages: (i) their small size allows the construction of portable, wearable, and low-cost products; (ii) the large surface-volume ratio enables the loading of a great number of biorecognition elements (e.g., probes, receptors); and (iii) direct contact of the recognition element with the analyte increases the sensitivity and specificity inducing low limits of detection (LOD). In this review, the role of nanostructured biosensors in miRNA detection is explored, focusing on electrochemical and optical sensing. In particular, four types of nanomaterials (metallic nanoparticles, graphene oxide, quantum dots, and nanostructured polymers) are reported for both detection strategies with the aim to show their distinct properties and applications.

Triple Negative Breast Cancer Preclinical Therapeutic Management by a Cationic Ruthenium-Based Nucleolipid Nanosystem.

Based on compelling preclinical evidence concerning the progress of our novel ruthenium-based metallotherapeutics, we are focusing research efforts on challenging indications for the treatment of invasive neoplasms such as the triple-negative breast cancer (TNBC). This malignancy mainly afflicts younger women, who are black, or who have a BRCA1 mutation. Because of faster growing and spreading, TNBC differs from other invasive breast cancers having fewer treatment options and worse prognosis, where existing therapies are mostly ineffective, resulting in a large unmet biomedical need. In this context, we benefited from an experimental model of TNBC both in vitro and in vivo to explore the effects of a biocompatible cationic liposomal nanoformulation, named HoThyRu/DOTAP, able to effectively deliver the antiproliferative ruthenium(III) complex AziRu, thus resulting in a prospective candidate drug. As part of the multitargeting mechanisms featuring metal-based therapeutics other than platinum-containing agents, we herein validate the potential of HoThyRu/DOTAP liposomes to act as a multimodal anticancer agent through inhibition of TNBC cell growth and proliferation, as well as migration and invasion. The here-obtained preclinical findings suggest a potential targeting of the complex pathways network controlling invasive and migratory cancer phenotypes. Overall, in the field of alternative chemotherapy to platinum-based drugs, these outcomes suggest prospective brand-new settings for the nanostructured AziRu complex to get promising goals for the treatment of metastatic TNBC.

A Proteomic Approach Reveals That miR-423-5p Modulates Glucidic and Amino Acid Metabolism in Prostate Cancer Cells.

Recently, we have demonstrated that miR-423-5p modulates the growth and metastases of prostate cancer (PCa) cells both in vitro and in vivo. Here, we have studied the effects of miR-423-5p on the proteomic profile in order to identify its intracellular targets and the affected pathways. Applying a quantitative proteomic approach, we analyzed the effects on the protein expression profile of miR-423-5p-transduced PCa cells. Moreover, a computational analysis of predicted targets of miR-423-5p was carried out by using several target prediction tools. Proteomic analysis showed that 63 proteins were differentially expressed in miR-423-5-p-transfected LNCaP cells if compared to controls. Pathway enrichment analysis revealed that stable overexpression of miR-423-5p in LNCaP PCa cells induced inhibition of glycolysis and the metabolism of several amino acids and a parallel downregulation of proteins involved in transcription and hypoxia, the immune response through Th17-derived cytokines, inflammation via amphorin signaling, and ion transport. Moreover, upregulated proteins were related to the S phase of cell cycle, chromatin modifications, apoptosis, blood coagulation, and calcium transport. We identified seven proteins commonly represented in miR-423-5p targets and differentially expressed proteins (DEPs) and analyzed their expression and influence on the survival of PCa patients from publicly accessible datasets. Overall, our findings suggest that miR-423-5p induces alterations in glucose and amino acid metabolism in PCa cells paralleled by modulation of several tumor-associated processes.

Sarcomatoid larynx carcinoma differential clinical evolution, on field statistical considerations.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.

LncRNAs and Immunity: Coding the Immune System with Noncoding Oligonucleotides.

Long noncoding RNAs (lncRNAs) represent key regulators of gene transcription during the inflammatory response. Recent findings showed lncRNAs to be dysregulated in human diseases, such as inflammatory bowel disease, diabetes, allergies, asthma, and cancer. These noncoding RNAs are crucial for immune mechanism, as they are involved in differentiation, cell migration and in the production of inflammatory mediators through regulating protein-protein interactions or their ability to assemble with RNA and DNA. The last interaction can occur in cis or trans and is responsible for all the possible lncRNAs biological effects. Our proposal is to provide an overview on lncRNAs roles and functions related to immunity and immune mediated diseases, since these elucidations could be beneficial to untangle the complex bond between them.

The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer.

Colorectal cancer (CRC) is the third most deadly cancer worldwide, and inflammatory bowel disease (IBD) is one of the critical factors in CRC carcinogenesis. IBD is responsible for an unphysiological and sustained chronic inflammation environment favoring the transformation. MicroRNAs (miRNAs) belong to a class of highly conserved short single-stranded segments (18-25 nucleotides) non-coding RNA and have been extensively discussed in both CRC and IBD. However, the role of miRNAs in the development of colitis-associated CRC (CAC) is less clear. The aim of this review is to summarize the major upregulated (miR-18a, miR-19a, miR-21, miR-31, miR-155 and miR-214) and downregulated (miR-124, miR-193a-3p and miR-139-5p) miRNAs in CAC, and their roles in genes' expression modulation in chronic colonic-inflammation-induced carcinogenesis, including programmed cell-death pathways. These miRNAs dysregulation could be applied for early CAC diagnosis, to predict therapy efficacy and for precision treatment.

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.

Insight toward the MicroRNA Profiling of Laryngeal Cancers: Biological Role and Clinical Impact.

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and accurate diagnosis of HNSCC is urgently demanded in order to prevent cancer progression and to improve the quality of the patient's life. Recently, microRNAs (miRNAs), a family of small non-coding RNAs, have been widely reported as new robust tools for prediction, diagnosis, prognosis, and therapeutic approaches of human diseases. Abnormally expressed miRNAs are strongly associated with cancer development, resistance to chemo-/radiotherapy, and metastatic potential through targeting a large variety of genes. In this review, we summarize on the recent reports that emphasize the pivotal biological roles of miRNAs in regulating carcinogenesis of HNSCC, particularly laryngeal cancer. In more detail, we report the characterized miRNAs with an evident either oncogenic or tumor suppressive role in the cancers. In addition, we also focus on the correlation between miRNA deregulation and clinical relevance in cancer patients. On the basis of intriguing findings, the study of miRNAs will provide a new great opportunity to access better clinical management of the malignancies.

Long Non-coding RNAs as Important Biomarkers in Laryngeal Cancer and Other Head and Neck Tumours.

Head and neck carcinoma (HNC) is a heterogeneous disease encompassing a variety of tumors according to the origin. Laryngeal cancer (LC) represents one of the most frequent tumors in the head and neck region. Despite clinical studies and advance in treatment, satisfactory curative strategy has not yet been reached. Therefore, there is an urgent need for the identification of specific molecular signatures that better predict the clinical outcomes and markers that serve as suitable therapeutic targets. Long non-coding RNAs (lncRNA) are reported as important regulators of gene expression and represent an innovative pharmacological application as molecular biomarkers in cancer. The purpose of this review is to discuss the most relevant epigenetic and histological prognostic biomarkers in HNC, with particular focus on LC. We summarize the emerging roles of long non-coding RNAs in HNC and LC development and their possible use in early diagnosis.

Whole-genome analysis suggesting probiotic potential and safety properties of Pediococcus pentosaceus DSPZPP1, a promising LAB strain isolated from traditional fermented sausages of the Basilicata region (Southern Italy).

Introduction: Many lactic acid bacteria (LAB) strains are currently gaining attention in the food industry and various biological applications because of their harmless and functional properties. Given the growing consumer demand for safe food, further research into potential probiotic bacteria is beneficial. Therefore, we aimed to characterize Pediococcus pentosaceus DSPZPP1, a LAB strain isolated from traditional fermented sausages from the Basilicata region of Southern Italy. Methods: In this study, we analyzed the whole genome of the P. pentosaceus DSPZPP1 strain and performed in silico characterization to evaluate its applicability for probiotics and use in the food industry. Results and Discussion: The whole-genome assembly and functional annotations revealed many interesting characteristics of the DSPZPP1 strain. Sequencing raw reads were assembled into a draft genome of size 1,891,398 bp, with a G + C content of 37.3%. Functional annotation identified 1930 protein-encoding genes and 58 RNAs including tRNA, tmRNA, and 16S, 23S, and 5S rRNAs. The analysis shows the presence of genes that encode water-soluble B-group vitamins such as biotin, folate, coenzyme A, and riboflavin. Furthermore, the analysis revealed that the DSPZPP1 strain can synthesize class II bacteriocin, penocin A, adding importance to the food industry for bio-enriched food. The DSPZPP1 genome does not show the presence of plasmids, and no genes associated with antimicrobial resistance and virulence were found. In addition, two intact bacteriophages were identified. Importantly, the lowest probability value in pathogenicity analysis indicates that this strain is non-pathogenic to humans. 16 s rRNA-based phylogenetic analysis and comparative analysis based on ANI and Tetra reveal that the DSPZPP1 strain shares the closest evolutionary relationship with P. pentosaceus DSM 20336 and other Pediococcus strains. Analysis of carbohydrate active enzymes (CAZymes) identified glycosyl transferases (GT) as a main class of enzymes followed by glycoside hydrolases (GH). Our study shows several interesting characteristics of the isolated DSPZPP1 strain from fermented Italian sausages, suggesting its potential use as a promising probiotic candidate and making it more appropriate for selection as a future additive in biopreservation.

MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer.

MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and in mechanisms of cancer growth and metastases. In this light, miRNAs could be promising therapeutic targets and biomarkers in clinical practice. Therefore, we investigated if specific miRNAs and their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease of miR-449a in LSCC patients with nodal metastases (63.3%) compared with patients without nodal involvement (44%). The AmpliSeq Transcriptome of HNO-210 miR-449a-transfected cell lines allowed the identification of IL6-R as a potential target. Moreover, the downregulation of IL6-R and the phosphorylation reduction of the downstream signaling effectors, suggested the inhibition of the IL-6 trans-signaling pathway. These biochemical effects were paralleled by a significant inhibition of invasion and migration in vitro and in vivo, supporting an involvement of epithelial-mesenchymal transition. These findings indicate that miR-449a contributes to suppress the metastasization of LSCC by the IL-6 trans-signaling block and affects sensitivity to external stimuli that mimic pro-inflammatory conditions.

Overview of current detection methods and microRNA potential in Clostridioides difficile infection screening.

Clostridioides difficile (formerly called Clostridium difficile, C. difficile) infection (CDI) is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and Prevention. Early detection and appropriate disease management appear to be essential. Meanwhile, although the majority of cases are hospital-acquired CDI, community-acquired CDI cases are also on the rise, and this vulnerability is not limited to immunocompromised patients. Gastrointestinal treatments and/or gastrointestinal tract surgeries may be required for patients diagnosed with digestive diseases. Such treatments could suppress or interfere with the patient's immune system and disrupt gut flora homeostasis, creating a suitable microecosystem for C. difficile overgrowth. Currently, stool-based non-invasive screening is the first-line approach to CDI diagnosis, but the accuracy is varied due to different clinical microbiology detection methods; therefore, improving reliability is clearly required. In this review, we briefly summarised the life cycle and toxicity of C. difficile, and we examined existing diagnostic approaches with an emphasis on novel biomarkers such as microRNAs. These biomarkers can be easily detected through non-invasive liquid biopsy and can yield crucial information about ongoing pathological phenomena, particularly in CDI.

Utility of psychotherapy assessed with Kessler scale in a population of cancer patients undergoing systemic oncological treatment: a mono-institutional experience.

BACKGROUND: Psychological distress has been associated with greater physical symptom severity, suffering, and mortality in cancer patients. For this reason, today, psychological care represents a fundamental tool for improving the quality of life of cancer patients. METHODS: From September 2021 to May 2022, 170 newly diagnosed cancer patients, were enrolled in the observational study at Medical Oncology Unit, "San Giovanni di Dio" Hospital. Before the start of oncological treatment, they were subjected to the Kessler 10 (K10) test, a validated measure of non-specific symptoms of psychological distress of the past 4 weeks. On the basis of the score, they were divided into three groups: low [10-19], moderate [20-29] and high [30-50] distress. After 3 months of psychological therapy, they repeated the test. RESULTS: Majority of patients were female (74.1%), aged <70 years (78.2%). The most represented tumours were breast (47.6%), colon (15.3%), urothelial (10.6%) and lung (7.6%) cancer and most patients started intravenous chemotherapy treatment (74.7%) rather than oral therapy. The previous remote pathological history and the family cancer history of the patients were also evaluated. Finally, marital status, schooling and employment status were recorded. At baseline we found 55, 72, and 43 patients with a low, moderate and high psychological distress, respectively. After the 3 months of psychotherapy, we re-administered the K10 test and we found a radical improvement in the degree of psychological distress (96 patients had a low score, 62 with a moderate score and just 12 patients with a high score). The great reduction in the score in K10 was statistically significant with a P value of <0.0001. The reduction of the K10 score was observed indiscriminately in all subgroups analysed. A statistically significant difference was observed between patients with different education levels (low 56% vs. high 32% of reduction in K10 score). Furthermore, the improvement in psychological health was greater in unemployed patients than in workers. CONCLUSIONS: The use of the K10 test is helpful in monitoring the degree of psychological distress of patients facing the diagnosis of cancer and who are about to start oncological treatment. Psychotherapy is effective in reducing the distress of these patients just a few months after starting treatment.

Clinical activity of regorafenib in elderly patients with recurrent glioblastoma.

Glioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.

Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer.

Nanodiamonds are innovative nanocrystalline carbon particles able to deliver chemically conjugated miRNAs. In oncology, the use of miRNA-based therapies may represent an advantage, based on their ability to simultaneously target multiple intracellular oncogenic targets. Here, nanodiamonds were tested and optimized to deliver miR-34a, a miRNA playing a key role in inhibiting tumor development and progression in many cancers. The physical-chemical properties of nanodiamonds were investigated suggesting electrical stability and uniformity of structure and size. Moreover, we evaluated nanodiamond cytotoxicity on two breast cancer cell models and confirmed their excellent biocompatibility. Subsequently, nanodiamonds were conjugated with miR-34a, using the chemical crosslinker polyethyleneimine; real-time PCR analysis revealed a higher level of miR-34a in cancer cells treated with the different formulations of nanodiamonds than with commercial transfectant. A significant and early nanodiamond-miR-34a uptake was recorded by FACS and fluorescence microscopy analysis in MCF7 and MDA-MB-231 cells. Moreover, nanodiamond-miR-34a significantly inhibited both cell proliferation and migration. Finally, a remarkable anti-tumor effect of miR-34a-conjugated nanodiamonds was observed in both heterotopic and orthotopic murine xenograft models. In conclusion, this study provides a rationale for the development of new therapeutic strategies based on use of miR-34a delivered by nanodiamonds to improve the clinical treatment of neoplasms.

MicroRNAs' Crucial Role in Salivary Gland Cancers' Onset and Prognosis.

Salivary gland cancer (SGC) is an uncommon and heterogeneous disease that accounts for around 8.5% of all head and neck cancers. MicroRNAs (miRNAs) consist of a class of highly conserved, short, single-stranded segments (18-25 nucleotides) of noncoding RNA that represent key gene-transcription regulators in physiological and pathological human conditions. However, their role in SGC development and progression is not completely clear. This review aims to compile and summarize the recent findings on the topic, focusing on the prognostic and diagnostic value of the major modulated and validated microRNAs in SGC. Their differential expression could possibly aid the clinician in delivering an early diagnosis, therapeutic strategy and precision medicine.

p53: From Fundamental Biology to Clinical Applications in Cancer.

p53 tumour suppressor gene is our major barrier against neoplastic transformation. It is involved in many cellular functions, including cell cycle arrest, senescence, DNA repair, apoptosis, autophagy, cell metabolism, ferroptosis, immune system regulation, generation of reactive oxygen species, mitochondrial function, global regulation of gene expression, miRNAs, etc. Its crucial importance is denounced by the high percentage of amino acid sequence identity between very different species (Homo sapiens, Drosophila melanogaster, Rattus norvegicus, Danio rerio, Canis lupus familiaris, Gekko japonicus). Many of its activities allowed life on Earth (e.g., repair from radiation-induced DNA damage) and directly contribute to its tumour suppressor function. In this review, we provide paramount information on p53, from its discovery, which is an interesting paradigm of science evolution, to potential clinical applications in anti-cancer treatment. The description of the fundamental biology of p53 is enriched by specific information on the structure and function of the protein as well by tumour/host evolutionistic perspectives of its role.

MiR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer.

BACKGROUND: The long non-coding RNA (lncRNA), MALAT1, plays a key role in the development of different cancers, and its expression is associated with worse prognosis in patients. However, its mechanism of action and its regulation are not well known in prostate cancer (PCa). A general mechanism of action of lncRNAs is their interaction with other epigenetic regulators including microRNAs (miRNAs). METHODS: Using lentiviral stable miRNA transfection together with cell biology functional assays and gene expression/target analysis, we investigated the interaction between MALAT1 and miR-423-5p, defined as a target with in silico prediction analysis, in PCa. RESULTS: Through bioinformatic analysis of data available from TCGA, we have found that MALAT1 expression correlates with high Gleason grade, metastasis occurrence, and reduced survival in PCa patients. These findings were validated on a TMA of PCa showing a significant correlation between MALAT1 expression with both stage and grading. We report that, in PCa cells, MALAT1 expression and activity is regulated by miR-423-5p that binds MALAT1, downregulates its expression and inhibits its activity in promoting proliferation, migration, and invasion. Using NanoString analysis, we unraveled downstream cell pathways that were affected by miR-423-5p expression and MALAT1 downregulation and identified several alterations in genes that are involved in metastatic response and angiogenic pathways. In addition, we showed that the overexpression of miR-423-5p increases survival and decreases metastases formation in a xenograft mouse model. CONCLUSIONS: We provide evidence on the role of MALAT1 in PCa tumorigenesis and progression. Also, we identify a direct interaction between miR-423-5p and MALAT1, which results in the suppression of MALAT1 action in PCa.