bims-mirpro Biomed News
on MiRNA as biomarker in prostate cancer diagnosis and prognosis
Issue of 2023–06–18
twenty-one papers selected by
Garima Jain, Banaras Hindu University



  1. Pathol Res Pract. 2023 Jun 12. pii: S0344-0338(23)00313-8. [Epub ahead of print]248 154613
      MicroRNAs (miRNAs; miRs) are small non-coding ribonucleic acids sequences vital in regulating gene expression. They are significant in many biological and pathological processes and are even detectable in various body fluids such as serum, plasma, and urine. Research has demonstrated that the irregularity of miRNA in multiplying cardiac cells is linked to developmental deformities in the heart's structure. It has also shown that miRNAs are crucial in diagnosing and progressing several cardiovascular diseases (CVDs). The review covers the function of miRNAs in the pathophysiology of CVD. Additionally, the review provides an overview of the potential role of miRNAs as disease-specific diagnostic and prognostic biomarkers for human CVD, as well as their biological implications in CVD.
    Keywords:  Cardiovascular diseases; Diagnosis; Epigenetic regulation; MiRNA; Prognosis; Transcriptional regulation
    DOI:  https://doi.org/10.1016/j.prp.2023.154613
  2. Int J Mol Sci. 2023 May 27. pii: 9360. [Epub ahead of print]24(11):
      Breast cancer is the most prevalent cancer in the world. Currently, the main treatments for breast cancer are radiotherapy, chemotherapy, targeted therapy and surgery. The treatment measures for breast cancer depend on the molecular subtype. Thus, the exploration of the underlying molecular mechanisms and therapeutic targets for breast cancer remains a hotspot in research. In breast cancer, a high level of expression of DNMTs is highly correlated with poor prognosis, that is, the abnormal methylation of tumor suppressor genes usually promotes tumorigenesis and progression. MiRNAs, as non-coding RNAs, have been identified to play key roles in breast cancer. The aberrant methylation of miRNAs could lead to drug resistance during the aforementioned treatment. Therefore, the regulation of miRNA methylation might serve as a therapeutic target in breast cancer. In this paper, we reviewed studies on the regulatory mechanisms of miRNA and DNA methylation in breast cancer from the last decade, focusing on the promoter region of tumor suppressor miRNAs methylated by DNMTs and the highly expressed oncogenic miRNAs inhibited by DNMTs or activating TETs.
    Keywords:  DNA methylation; breast cancer; drug resistance; miRNA
    DOI:  https://doi.org/10.3390/ijms24119360
  3. Cells. 2023 May 29. pii: 1498. [Epub ahead of print]12(11):
      Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRNAs' roles in physiological and pathological conditions, such as the development of cancer and respiratory, neurodegenerative, and cardiovascular diseases following exposure to various environmental stressors.
    Keywords:  air pollution; biomarkers; extracellular vesicles; heat shock proteins; liquid biopsy; non-coding RNAs; personalized medicine; stress
    DOI:  https://doi.org/10.3390/cells12111498
  4. Cell Mol Biol (Noisy-le-grand). 2023 Mar 31. 69(3): 92-97
      Prostate cancer refers to the epithelial malignant tumor of the prostate. It has a high incidence and mortality rate, seriously endangering the lives of men. In recent years, lncRNAs have become a hot topic for lots of scholars for their regulation functions on assorted cancers. Several lncRNAs have been proven they can take part in the regulation of prostate cancer development. Nevertheless, how HOXA11-AS (homeobox A11 antisense RNA)functioned in prostate cancer is not explained. In our research, the expression of HOXA11-AS in prostate cancer cells was evaluated through qRT-PCR. Colony formation experiments, EdU experiments, Tanswelland TUNEL experiments, as well as caspase-3 detection, were designed to test cell proliferation, migration, invasion and apoptosis. RIP, pull down and luciferase reporter experiments examined the correlations of HOXA11-AS, miR-148b-3p and MLPH. We discovered a high level of HOXA11-AS in prostate cancer cells.HOXA11-AS silence could restrain the mentioned cell malignant behavior. Mechanically, HOXA11-AS could sponge miR-148b-3p to target MLPH. MLPH was positively associated with HOXA11-AS and overexpressed it accelerated the progression of prostate cancer. Taken together, HOXA11-AS elevated MLPH expression by sponging miR-148b-3p and accelerated prostate cancer cell proliferation.
    DOI:  https://doi.org/10.14715/cmb/2023.69.3.12
  5. Pathol Res Pract. 2023 Jun 08. pii: S0344-0338(23)00310-2. [Epub ahead of print]248 154610
      Noncoding RNAs are a type of cellular RNA not having the ability to translate into proteins. As an important type of ncRNA with a length of about 22 nucleotides (nt), microRNAs were revealed to contribute to regulating the various cellular functions via regulating the protein translation of target genes. Among them, available studies proposed that miR-495-3p is a pivotal player in cancer pathogenesis. These studies showed that the expression level of miR-495-3p decreased in various cancer cells, suggesting its tumor suppressor role in cancer pathogenesis. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are the important regulators of miR-495-3p via sponging it, leading to increased expression levels of its target genes. Moreover, miR-495-3p was shown to have a promising potential to be a prognostic and diagnostic biomarker in cancer. MiR-495-3p also could affect the resistance of cancer cells to chemotherapy agents. Here, we discussed the molecular mechanisms of miR-495-3p in various cancer including breast cancer. In addition, we discussed the miR-495-3p potential as a prognostic and diagnostic biomarker as well as its activity in cancer chemotherapy. Finally, we discussed the current limitations regarding the use of microRNAs in clinics and the future prospects of microRNAs.
    Keywords:  Biomarker; Cancer; MiR-495–3p; Tumor suppressor
    DOI:  https://doi.org/10.1016/j.prp.2023.154610
  6. Oncoimmunology. 2023 ;12(1): 2221081
      Natural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells. However, the involvement of exosomal miRNAs in the function of NK exosomes is poorly understood. In this study, we explored the miRNA content of NK exosomes by microarray as compared to their cellular counterparts. The expression of selected miRNAs and lytic potential of NK exosomes against childhood B acute lymphoblastic leukemia cells after co-cultures with pancreatic cancer cells were also evaluated. We identified a small subset of miRNAs, including miR-16-5p, miR-342-3p, miR-24-3p, miR-92a-3p and let-7b-5p that is highly expressed in NK exosomes. Moreover, we provide evidence that NK exosomes efficiently increase let-7b-5p expression in pancreatic cancer cells and induce inhibition of cell proliferation by targeting the cell cycle regulator CDK6. Let-7b-5p transfer by NK exosomes could represent a novel mechanism by which NK cells counteract tumor growth. However, both cytolytic activity and miRNA content of NK exosomes were reduced upon co-culture with pancreatic cancer cells. Alteration in the miRNA cargo of NK exosomes, together with their reduced cytotoxic activity, could represent another strategy exerted by cancer to evade the immune response. Our study provides new information on the molecular mechanisms used by NK exosomes to exert anti-tumor-activity and offers new clues to integrate cancer treatments with NK exosomes.
    Keywords:  Natural killer cells; exosomes; gene expression profiling; microRNA; tumor microenvironment
    DOI:  https://doi.org/10.1080/2162402X.2023.2221081
  7. PLoS One. 2023 ;18(6): e0286996
      Ets-related gene (ERG) is overexpressed as a fusion protein in prostate cancer. During metastasis, the pathological role of ERG is associated with cell proliferation, invasion, and angiogenesis. Here, we hypothesized that miRNAs regulate ERG expression through its 3'UTR. Several bioinformatics tools were used to identify miRNAs and their binding sites on 3'UTR of ERG. The selected miRNAs expression was analyzed in prostate cancer samples by qPCR. The miRNAs overexpression was induced in prostate cancer cells (VCaP) to analyze ERG expression. Reporter gene assay was performed to evaluate the ERG activity in response to selected miRNAs. The expression of ERG downstream target genes was also investigated through qPCR after miRNAs overexpression. To observe the effects of selected miRNAs on cell proliferation and migration, scratch assay was performed to calculate the cell migration rate. miR-4482 and miR-3912 were selected from bioinformatics databases. miR-4482 and -3912 expression were decreased in prostate cancer samples, as compared to controls (p<0.05 and p<0.001), respectively. Overexpression of miR-4482 and miR-3912 significantly reduced ERG mRNA (p<0.001 and p<0.01), respectively) and protein (p<0.01) in prostate cancer cells. The transcriptional activity of ERG was significantly reduced (p<0.01) in response to miR-4482 and-3912. ERG angiogenic targets and cell migration rate was also reduced significantly (p<0.001) after miR-4482 and -3912 over-expression. This study indicates that miR-4482 and -3912 can suppress the ERG expression and its target genes, thereby, halt prostate cancer progression. These miRNAs may be employed as a potential therapeutic target for the miRNA-based therapy against prostate cancer.
    DOI:  https://doi.org/10.1371/journal.pone.0286996
  8. Pathol Res Pract. 2023 Jun 07. pii: S0344-0338(23)00290-X. [Epub ahead of print]248 154590
      Cancer of the salivary glands is one of the five major types of head and neck cancer. Due to radioresistance and a strong propensity for metastasis, the survival rate for nonresectable malignant tumors is dismal. Hence, more research is needed on salivary cancer's pathophysiology, particularly at the molecular level. The microRNAs (miRNAs) are a type of noncoding RNA that controls as many as 30% of all genes that code for proteins at the posttranscriptional level. Signature miRNA expression profiles have been established in several cancer types, suggesting a role for miRNAs in the incidence and progression of human malignancies. Salivary cancer tissues were shown to have significantly aberrant levels of miRNAs compared to normal salivary gland tissues, supporting the hypothesis that miRNAs play a crucial role in the carcinogenesis of salivary gland cancer (SGC). Besides, several SGC research articles reported potential biomarkers and therapeutic targets for the miRNA-based treatment of this malignancy. In this review, we will explore the regulatory impact of miRNAs on the processes underlying the molecular pathology of SGC and provide an up-to-date summary of the literature on miRNAs that impacted this malignancy. We will eventually share information about their possible use as diagnostic, prognostic, and therapeutic biomarkers in SGC.
    Keywords:  Biomarkers; Diagnostic; Prognostic; Salivary gland cancer; microRNA
    DOI:  https://doi.org/10.1016/j.prp.2023.154590
  9. Int J Mol Sci. 2023 May 25. pii: 9240. [Epub ahead of print]24(11):
      Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer.
    Keywords:  apoptosis; cancer cell death; flavones; flavonoids; prostate cancer
    DOI:  https://doi.org/10.3390/ijms24119240
  10. Microbes Infect. 2023 Jun 14. pii: S1286-4579(23)00076-X. [Epub ahead of print] 105173
      Chandipura virus (CHPV) belongs to the family Rhabdoviridae and has a single stranded RNA genome that causes encephalitis among children in India's tropical states. Activation of the antiviral immune response upon viral infection is important for the host's defense. In response to CHPV infection, the brain resident macrophages (microglial cells) control the pathogenic insults. The microRNAs (miRNAs) are 22 nts non-coding RNAs that serve as delicate regulators of their target genes at post-transcriptional level. In this study, we explored miR-155 mediated antiviral response in CHPV infected human microglial cells. The gene and protein expression patterns were studied through quantitative real-time PCR (qPCR) and immunoblotting respectively. Additionally, miRNA target validation was done by overexpression and knockdown of miR-155. We observed increased expression of miR-155 in CHPV infected human microglial cells. The upregulated miR-155 supresses the Suppressor of Cytokine Signalling 1 (SOCS1). Reduced SOCS1 in turn led to enhanced phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and induction of Interferon-β (IFN-β), which promoted the expression of IFN-stimulated gene 54 (ISG54) and IFN-stimulated gene 56 (ISG56). In this study, miR-155 positively modulated the cellular antiviral response by enhancing type I IFN signalling through inhibition of SOCS1 in CHPV infected microglial cells.
    Keywords:  Chandipura virus; antiviral response; microRNA; microglia
    DOI:  https://doi.org/10.1016/j.micinf.2023.105173
  11. Cancers (Basel). 2023 May 25. pii: 2903. [Epub ahead of print]15(11):
      MicroRNAs (miRNAs) play a critical role in the regulation of mRNA stability and translation. In spite of our present knowledge on the mechanisms of mRNA regulation by miRNAs, the utilization and translation of these ncRNAs into clinical applications have been problematic. Using hsa-miR-429 as an example, we discuss the limitations encountered in the development of efficient miRNA-related therapies and diagnostic approaches. The miR-200 family members, which include hsa-miR-429, have been shown to be dysregulated in different types of cancer. Although these miR-200 family members have been shown to function in suppressing epithelial-to-mesenchymal transition, tumor metastasis, and chemoresistance, the experimental results have often been contradictory. These complications involve not only the complex networks involving these noncoding RNAs, but also the problem of identifying false positives. To overcome these limitations, a more comprehensive research strategy is needed to increase our understanding of the mechanisms underlying their biological role in mRNA regulation. Here, we provide a literature analysis of the verified hsa-miR-429 targets in various human research models. A meta-analysis of this work is presented to provide better insights into the role of hsa-miR-429 in cancer diagnosis and any potential therapeutic approach.
    Keywords:  RNAi drug candidates; RNAi therapy; microRNAs; ncRNAs; off-target effects; siRNAs
    DOI:  https://doi.org/10.3390/cancers15112903
  12. Cancers (Basel). 2023 May 23. pii: 2885. [Epub ahead of print]15(11):
      Prostate cancer is the most frequent malignant tumor in men, and, despite the great improvements in survival in patients with localized cancer, the prognosis for metastatic disease remains poor. Novel molecular targeted therapies, which block specific molecules or signaling pathways in tumor cells or in their microenvironment, have shown encouraging results in metastatic castration-resistant prostate cancer. Among these therapeutic approaches, prostate-specific membrane antigen-targeted radionuclide therapies and DNA repair inhibitors represent the most promising ones, with some therapeutic protocols already approved by the FDA, whereas therapies targeting tumor neovascularization and immune checkpoint inhibitors have not yet demonstrated clear clinical benefits. In this review, the most relevant studies and clinical trials on this topic are illustrated and discussed, together with future research directions and challenges.
    Keywords:  anti-angiogenic therapy; castration-resistant prostate cancer; immunotherapy; metastasis; molecular targeted therapies
    DOI:  https://doi.org/10.3390/cancers15112885
  13. Clin Chim Acta. 2023 Jun 12. pii: S0009-8981(23)00247-4. [Epub ahead of print] 117445
      Over the last decade, increasing research has focused on urinary exosomes (UEs) in biological fluids and their relationship with physiological and pathological processes. UEs are membranous vesicles with a size of 40-100 nm, containing a number of bioactive molecules such as proteins, lipids, mRNAs, and miRNAs. These vesicles are an inexpensive non-invasive source that can be used in clinical settings to differentiate healthy patients from diseased patients, thereby serving as potential biomarkers for the early identification of disease. Recent studies have reported the isolation of small molecules called exosomal metabolites from individuals' urine with different diseases. These metabolites could utilize for a variety of purposes, such as the discovery of biomarkers, investigation of mechanisms related to disease development, and importantly prediction of cardiovascular diseases (CVDs) risk factors, including thrombosis, inflammation, oxidative stress, hyperlipidemia as well as homocysteine. It has been indicated that alteration in urinary metabolites of N1-methylnicotinamide, 4-aminohippuric acid, and citric acid can be valuable in predicting cardiovascular risk factors, providing a novel approach to evaluating the pathological status of CVDs. Since the UEs metabolome has been clearly and precisely so far unexplored in CVDs, the present study has specifically addressed the role of the mentioned metabolites in the prediction of CVDs risk factors.
    Keywords:  Cardiovascular diseases; Cardiovascular risk factors; Urinary exosomal metabolites; Urinary exosomes
    DOI:  https://doi.org/10.1016/j.cca.2023.117445
  14. Minerva Dent Oral Sci. 2023 Jun 16.
       BACKGROUND: Head and neck cancer (HNC) is the seventh most prevalent type of cancer in the globe, and it encompasses a wide range of tumors that affect the oral, facial and neck region. Despite breakthroughs in treatment strategies, patients survival has not increased substantially in the last few decades. Therefore, there is need for quick and reliable biomarkers and therapeutic targets for the treatment of HNC. Interestingly, microRNAs (miRNAs) are a small non-coding RNAs (ncRNAs) that have a role in the post-transcriptional regulation of gene expression. Thus, the aim of the study is to evaluate the role of miR-7-3p in the HNC and normal tissues.
    METHODS: A total of 25 HNC and normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals. Bioinformatic tool (TargetScan) was used to predict the target for miR-7-3p. The tissue samples were processed for Hematoxylin and Eosin staining and following that total RNA was extracted and analyzed for expression studies using RT-qPCR.
    RESULTS: The bioinformatic analysis of the current study have revealed that STAT3 is a direct target for miR-7-3p. The histopathological examination showed damaged epithelial cells and keratin pool formation was observed in HNC tissue. Our results have also revealed that the miR-7-3p levels were significantly reduced and STAT3 levels were significantly higher in the HNC tissues when compared to the normal tissues.
    CONCLUSIONS: MiR-7-3p can be used as a prognostic, diagnostic biomarker and therapeutic target for the treatment of HNC.
    DOI:  https://doi.org/10.23736/S2724-6329.23.04824-6
  15. Gene. 2023 Jun 07. pii: S0378-1119(23)00359-1. [Epub ahead of print]877 147518
      MicroRNAs (miRNAs) are a class of single-stranded small non-coding RNAs with a length of 21-23 nucleotides. One such miRNA, miR-492, is located in the KRT19 pseudogene 2 (KRT19P2) of chromosome 12q22 and can also be generated from the processing of the KRT19 transcript at chromosome 17q21. Aberrant expression of miR-492 has been observed in cancers of various physiological systems. miR-492 has been shown to target at least 11 protein-coding genes, which are involved in the regulation of cellular behaviors such as growth, cell cycle, proliferation, epithelial- mesenchymal transition (EMT), invasion and migration. The expression of miR-492 can be regulated by both endogenous and exogenous factors. Furthermore, miR-492 is involved in the regulation of several signaling pathways including the PI3K/AKT signaling pathway, WNT/β-catenin signaling pathway, and MAPK signaling pathway. High expression of miR-492 has been closely associated with shorter overall survival in patients with gastric cancer, ovarian cancer, oropharyngeal carcinoma, colorectal cancer, and hepatocellular carcinoma. This study systematically summarizes the related research findings on miR-492, providing potential insights for future investigations.
    DOI:  https://doi.org/10.1016/j.gene.2023.147518
  16. Cell Mol Biol (Noisy-le-grand). 2023 Mar 31. 69(3): 69-74
      MicroRNAs (miRNAs) were reportedly demonstrated to participate in ovarian cancer (OC) progression. Here, we inquired into the role of miR-188-5punderneath OC cell proliferation and migration. In this respect, our work examined the miR-188-5p expression and demonstrated its expression level in OC by qRT-PCR analysis. Enforced miR-188-5p expression resulted in a serious downfall of cell growth and mobility, and acceleration apoptosis in OC cells. Furthermore, we identified CCND2 as a target gene of miR-188-5p. RIP assay and luciferase reporter assay verified the interaction of miR-188-5p and CCND2 and exhibited that miR-188-5p greatly hindered the expression of CCND2. Besides, HuR stabilized CCND2 mRNA and counteracted the miR-188-5p suppressive effect on CCND2 mRNA. Functionally, rescue experiments also showed that miR-188-5p-mediated suppression on OC cell proliferation and migration was reverted by CCND2 or HuR overexpression. Our study found miR-188-5p was a tumor suppressor in OC via competing for CCND2 with ELAVL1, contributing to coming up with novel clues for OC therapies.
    DOI:  https://doi.org/10.14715/cmb/2023.69.3.9
  17. Transl Cancer Res. 2023 May 31. 12(5): 1359-1362
      
    Keywords:  biomarkers; cancer; microRNA; small extracellular vesicles
    DOI:  https://doi.org/10.21037/tcr-23-46
  18. Int J Mol Sci. 2023 May 25. pii: 9282. [Epub ahead of print]24(11):
      Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG. The most significantly affected biological processes in the samples were also identified, so that they may be further studied in the search for new potential therapeutic targets for the categories of PCa under consideration. The highest predictive potential was found with the EEF1A1P5, RPLP0P6, ZNF483, CIBAR1, HECTD2, OGN, and CLIC4 genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa-Gleason Score 7 (groups 2 and 3 according to the ISUP classification)-on the basis of which the LPL, MYC, and TWIST1 genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation.
    Keywords:  ISUP; RNA-Seq; TMPRSS2-ERG; gene expression; heterogeneity; molecular subtype; pathways; prostate cancer; risk groups; transcriptome
    DOI:  https://doi.org/10.3390/ijms24119282
  19. Pathol Res Pract. 2023 Jun 12. pii: S0344-0338(23)00312-6. [Epub ahead of print]248 154612
      Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.
    Keywords:  Diagnosis; MiRNA; Prognosis; Testicular cancer, Drug resistance; Testicular germ cell tumors (TGCTs)
    DOI:  https://doi.org/10.1016/j.prp.2023.154612
  20. PeerJ. 2023 ;11 e15409
      The postmortem interval (PMI) is the time elapsing since the death of an individual until the body is examined. Different molecules have been analyzed to better estimate the PMI with variable results. The miRNAs draw attention in the forensic field to estimate the PMI as they can better support degradation. In the present work, we analyzed the miRNome at early PMI in rats' skeletal muscle using the Affymetrix GeneChip™ miRNA 4.0 microarrays. We found 156 dysregulated miRNAs in rats' skeletal muscle at 24 h of PMI, out of which 84 were downregulated, and 72 upregulated. The miRNA most significantly downregulated was miR-139-5p (FC = -160, p = 9.97 × 10-11), while the most upregulated was rno-miR-92b-5p (FC = 241.18, p = 2.39 × 10-6). Regarding the targets of these dysregulated miRNAs, the rno-miR-125b-5p and rno-miR-138-5p were the miRNAs with more mRNA targets. The mRNA targets that we found in the present study participate in several biological processes such as interleukin secretion regulation, translation regulation, cell growth, or low oxygen response. In addition, we found a downregulation of SIRT1 mRNA and an upregulation of TGFBR2 mRNA at 24 h of PMI. These results suggest there is an active participation of miRNAs at early PMI which could be further explored to identify potential biomarkers for PMI estimation.
    Keywords:  Microarrays; Non-coding RNA; Postmortem interval; miRNA
    DOI:  https://doi.org/10.7717/peerj.15409
  21. Front Cardiovasc Med. 2023 ;10 1202187
      Extracellular vesicles (EVs) are small, lipid bilayer-enclosed structures released by various cell types that play a critical role in intercellular communication. In atherosclerosis, EVs have been implicated in multiple pathophysiological processes, including endothelial dysfunction, inflammation, and thrombosis. This review provides an up-to-date overview of our current understanding of the roles of EVs in atherosclerosis, emphasizing their potential as diagnostic biomarkers and their roles in disease pathogenesis. We discuss the different types of EVs involved in atherosclerosis, the diverse cargoes they carry, their mechanisms of action, and the various methods employed for their isolation and analysis. Moreover, we underscore the importance of using relevant animal models and human samples to elucidate the role of EVs in disease pathogenesis. Overall, this review consolidates our current knowledge of EVs in atherosclerosis and highlights their potential as promising targets for disease diagnosis and therapy.
    Keywords:  EV tracking models; atherosclerosis; biomarkers; extracellular vesicles; therapeutics
    DOI:  https://doi.org/10.3389/fcvm.2023.1202187