A.M. Abdelhamid , Y. Zeinelabdeen , T. Manie , E. Khallaf , R.A. Assal , R.A. Youness
{"title":"miR-17–5p/STAT3/H19: A novel regulatory axis tuning ULBP2 expression in young breast cancer patients","authors":"A.M. Abdelhamid , Y. Zeinelabdeen , T. Manie , E. Khallaf , R.A. Assal , R.A. Youness","doi":"10.1016/j.prp.2024.155638","DOIUrl":"10.1016/j.prp.2024.155638","url":null,"abstract":"<div><h3>Background and aim</h3><div>UL-16 binding protein 2 (ULBP2) is a highly altered ligand for the activating receptor, NKG2D in breast cancer (BC). However, the mechanism behind its de-regulation in BC patients remains to be explored. The sophisticated crosstalk between miR-17–5p, the lncRNA H19, and STAT3 as a possible upstream regulatory loop for ULBP2 in young BC patients and cell lines remains as an unexplored area. Therefore, this study aimed at unravelling the ncRNA circuit regulating ULBP2 in young BC patients and cell lines.</div></div><div><h3>Patients and methods</h3><div>A total of 30 BC patients were recruited for this study. The expression levels of miR-17–5p, lncRNA H19, and STAT3 were examined in 30 BC tissues compared to their normal counterparts. In addition, the expression signatures of those transcripts were compared in young (<40 years) and old BC (≥40 years) patients. miR-17–5p oligonucleotides, STAT3 and H19 siRNAs were transfected in MDA-MB-231 cells using HiPerfect® Transfection Reagent. miR-17–5p and the transcripts of the target genes quantified using RT-qPCR. Their relative expression was calculated using the 2<sup>–ΔΔCT</sup> method.</div></div><div><h3>Results</h3><div>Through acting as a ceRNA circuit that antagonizes the function of miR-17–5p, H19 prevented the miR-17–5p-induced downregulation of STAT3; this mechanism further contributes to the pathogenesis of BC. Ectopic expression of miR-17–5p in MDA-MB-231 cells displayed its prominent role as an indirect potential activator of NK cells by significantly repressing the expression levels of the oncogenic mediator STAT3 and the oncogenic lncRNA H19 and inducing ULBP2 expression level by 3 folds in TNBC cell lines compared to mock cells. Furthermore, knocking down of STAT3 repressed the lncRNA H19 and increased ULBP2 expression levels, whereas siRNAs against H19 increased the expression levels of ULBP2.</div></div><div><h3>Conclusion</h3><div>This study highlighted the crosstalk between the novel regulatory network composed of miR-17–5p, H19 and STAT3, and their impact on ULBP2 in BC. Moreover, this study underscored the potential role of miR-17–5p in counteracting the immune evasion tactics, particularly the shedding of ULBP2 in young BC patients, through the modulation of the STAT3/H19/ULBP2 regulatory axis. Thus, targeting this novel regulatory network could potentially enhance our understanding and advance the future application of the innate system-mediated immunotherapy in BC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155638"},"PeriodicalIF":2.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adil Aziz Khan , Naveen Kumar R , Sushanta Chakma , Sumanta Das
{"title":"Sarcoma diagnosis by DNA methylation classifier: A systematic review, current status and future prospects","authors":"Adil Aziz Khan , Naveen Kumar R , Sushanta Chakma , Sumanta Das","doi":"10.1016/j.prp.2024.155634","DOIUrl":"10.1016/j.prp.2024.155634","url":null,"abstract":"<div><div>Sarcomas, a diverse group of malignant tumors originating from connective tissues, present substantial diagnostic challenges due to their histological heterogeneity. Traditional diagnostic methods include histomorphology along with immunohistochemistry is necessary for primary evaluation. Fluorescence in situ hybridization (FISH) is a supplementary tool that helps with additional findings. However it is very difficult sometimes to accurately classify sarcoma subtypes despite all these tools. Recent advancements in DNA methylation profiling have emerged as a promising approach to enhance the precision of sarcoma diagnosis. This paper delves into the role of DNA methylation classifiers in diagnosing sarcomas, emphasizing their potential to improve diagnostic accuracy, inform treatment decisions, and ultimately enhance patient outcomes.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155634"},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abulfazl Vatankhah , Sepehr Hoseinzadeh Moghaddam , Sadaf Afshari , Amir R. Afshari , Prashant Kesharwani , Amirhossein Sahebkar
{"title":"Recent update on anti-tumor mechanisms of valproic acid in glioblastoma multiforme","authors":"Abulfazl Vatankhah , Sepehr Hoseinzadeh Moghaddam , Sadaf Afshari , Amir R. Afshari , Prashant Kesharwani , Amirhossein Sahebkar","doi":"10.1016/j.prp.2024.155636","DOIUrl":"10.1016/j.prp.2024.155636","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is a malignant tumor of the brain that is considered to be incurable. Currently, surgical removal of tumors, chemotherapy with temozolomide, and radiation treatment remain established options for treatment. Nevertheless, the prognosis of those with GBM continues to be poor owing to the inherent characteristics of tumor growth and spread, as well as the resistance to treatment. To effectively deal with the present circumstances, it is vital to do extensive study to understand GBM thoroughly. The following piece provides a concise overview of the most recent advancements in using valproic acid, an antiseizure medication licensed by the FDA, for treating GBM. In this review, we outline the most recent developments of valproic acid in treating GBM, as well as its fundamental mechanisms and practical consequences. Our goal is to provide a greater understanding of the clinical use of valproic acid as a potential therapeutic agent for GBM.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155636"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sruthi Babu , Michael Horowitz , Lyanne A. Delgado-Coka , Lucia Roa-Peña , Ali Akalin , Luisa F. Escobar-Hoyos , Kenneth R. Shroyer
{"title":"Keratin 17 and A2ML1 are negative prognostic biomarkers in non-small cell lung cancer","authors":"Sruthi Babu , Michael Horowitz , Lyanne A. Delgado-Coka , Lucia Roa-Peña , Ali Akalin , Luisa F. Escobar-Hoyos , Kenneth R. Shroyer","doi":"10.1016/j.prp.2024.155643","DOIUrl":"10.1016/j.prp.2024.155643","url":null,"abstract":"<div><div>Although the overall prognosis for patients with non-small cell lung cancer (NSCLC) has improved over the past several decades, there are still survival differences that are not accurately defined by clinicopathological factors. Thus, there is an unmet clinical need to develop novel approaches to enhance prognostic accuracy for these patients. Keratin 17 (K17) is a negative prognostic biomarker in a wide range of cancer types, including pancreatic ductal adenocarcinoma, head and neck squamous cell carcinoma, and pulmonary adenocarcinoma (LUAD), but has yet to be investigated as a prognostic biomarker in primary lung squamous cell carcinoma (LSCC). Based on TCGA RNA-seq data, alpha-2-macroglobulin like 1 (A2ML1), a protease inhibitor, is highly correlated with K17 in other solid tumors, including pancreatic ductal adenocarcinoma and is also a prognostic biomarker for LSCC, although the prognostic accuracy of A2ML1 for LUAD has not been tested. Thus, we hypothesized that A2ML1 expression correlates with K17 expression and that K17/A2ML1 co-testing could provide complementary prognostic data for NSCLC. The aims of this study were to explore K17 and A2ML1 as dual prognostic biomarkers, using publicly available gene expression databases [The Cancer Genome Atlas (TCGA)] LSCC (n=266), LUAD (n=271)] and multiplexed immunohistochemistry (mIHC) on representative sections of LSCC (n=104) and LUAD (n=107) from two major academic medical centers. Our results suggest that using either mRNA or mIHC-based methods, combined K17 and A2ML1 testing provides information, independent of other clinicopathologic variables, that could impact treatment decisions for patients with NSCLC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155643"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renata Dellalibera-Joviliano , Marcelo E. Garcia , Mozart Marins , Ana L.úcia Fachin , Lucélio B. Couto , Edgar Mesquita , Tatiana T. Komoto , Gabriel Silva , Walter Campos Neto , Leonardo Orlando , Marina Durand , Suzelei C. França , Reinaldo B. Bestetti
{"title":"Interleukin-12 treatment reduces tumor growth and modulates the expression of CASKA and MIR-203 in athymic mice bearing tumors induced by the HGC-27 gastric cancer cell line","authors":"Renata Dellalibera-Joviliano , Marcelo E. Garcia , Mozart Marins , Ana L.úcia Fachin , Lucélio B. Couto , Edgar Mesquita , Tatiana T. Komoto , Gabriel Silva , Walter Campos Neto , Leonardo Orlando , Marina Durand , Suzelei C. França , Reinaldo B. Bestetti","doi":"10.1016/j.prp.2024.155625","DOIUrl":"10.1016/j.prp.2024.155625","url":null,"abstract":"<div><div>Gastric cancer (GC) is one of the most common malignant tumors in the digestive system and due to its poor prognosis, there is an increase in the demand for more effective anticancer therapies. Interleukins are potential anticancer agents which can modulate expression of cancer related genes and have therapeutic effects. Interleukin 12 (IL-12) exhibits potent anti-tumor, anti-angiogenic and anti-metastatic activities and represents the ideal candidate for tumor immunotherapy, due to its ability to activate both innate and adaptive immunities. The aim of this study was to evaluate the effect of IL-12 administration on GC tumor growth induced in the cancer xenograft nude mouse model. Tumor development was analyzed weekly and after 8 weeks, the animals were sacrificed for cytokine analysis (IL-4, TNF-alfa, IL-2, INF-gamma, IL-12, IL-10, TGF-beta) by ELISA. The tumor cells in the implanted areas of the animals that developed solid growth of the tumor (anatomopathological analysis was performed). We have also evaluated CASK and miR203 expression, two related cell invasion factors, in the induced tumors after administration of 6 n/kg IL-12. The development of tumor masses was observed in all groups of animals inoculated with HGC-27 neoplastic cells. In animals treated with 6 n/kg IL-12, there was no tumor development confirmed by anatomopathological analysis. Changes in the levels of pro and anti-inflammatory cytokines were also observed. Our results indicated that miR203 expression was elevated while CASK was downregulated. These results suggest that IL-12 treatment repress the tumor growth by induction of miR203 expression which in turn repress CASK expression.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155625"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of estradiol in inducing endometrial cancer using RL95-2","authors":"Anuja Pant, Kareena Moar, Pawan Kumar Maurya","doi":"10.1016/j.prp.2024.155640","DOIUrl":"10.1016/j.prp.2024.155640","url":null,"abstract":"<div><h3>Background</h3><div>Endometrial cancer is the most common gynecological malignancy that originates from the inner lining of the uterus and predominantly affects postmenopausal women. Prolonged exposure to estrogen, family history of endometrial cancer, obesity, and hormonal imbalance are some of the risk factors associated with endometrial cancer. In our study, we investigated the effect of estradiol, a potent form of estrogen at various concentrations on endometrial cell line RL95–2.</div></div><div><h3>Methods</h3><div>Endometrial cell RL95–2 were cultured in DMEM medium with optimal conditions required to maintain the cells. MTT assay and colony formation assay were further performed after treating the cells with different concentrations of estradiol (1, 10, and 100 nM) and TAM (100 nM). Moreover, the effect of genes regulated by estradiol was also examined using microarray and validated using real-time polymerase chain reaction (qRT-PCR).</div></div><div><h3>Results</h3><div>Time-dependent MTT assay shows a significant change in the ability of the cells to survive relative to concentrations. Colony formation was found to be directly proportional to the concentration of the estradiol (p < 0.05). Among genes, <em>MMP14</em> (p = 0.03), <em>SPARCL1</em> (p = 0.005), and <em>CLU</em> (p = 0.06) showed a significant up-regulation in their expression after estradiol treatment while <em>NRN1</em> (p < 0.001) showed significant downregulation in expression pattern compared to control. However, the TAM treatment was found to be significantly effective after 72 h (p < 0.001) compared to control and 100 nM E2 (p = 0.0206).</div></div><div><h3>Conclusion</h3><div>Our study suggests that estradiol significantly contributes to regulating the viability, colony formation, and expression of genes associated with endometrial cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155640"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roberta Queiroz da Silvia Lima , César Freire Melo Vasconcelos , João Pedro Alves Gomes , Erika da Silva Bezerra de Menezes , Barbara de Oliveira Silva , Claudio Montenegro , Sérgio de Sá Leitão Paiva Júnior , Michelly Cristiny Pereira
{"title":"miRNA-21, an oncomiR that regulates cell proliferation, migration, invasion and therapy response in lung cancer","authors":"Roberta Queiroz da Silvia Lima , César Freire Melo Vasconcelos , João Pedro Alves Gomes , Erika da Silva Bezerra de Menezes , Barbara de Oliveira Silva , Claudio Montenegro , Sérgio de Sá Leitão Paiva Júnior , Michelly Cristiny Pereira","doi":"10.1016/j.prp.2024.155601","DOIUrl":"10.1016/j.prp.2024.155601","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related death globally, with poor survival rates due mostly to a lack of early detection. The usual diagnostic technique includes a biopsy, which is frequently performed later in the disease's progression. In order to uncover processes that improve illness detection and prognosis, miRNA-21 emerges as a major miRNA identified in a variety of cancer types, including lung cancer. This review compiles insights into the involvement of miRNA-21 within the distinct cellular processes underlying lung cancer. To achieve this, we conducted an extensive literature review, drawing from published in vitro, in vivo and clinical trials studies. Searches were performed in the PubMed, Scielo, CAPES Journal Portal, BVS, INCA, and Clinical Trials.Gov. Only English written articles were selected. As screening criteria, we selected articles that explored the modulation pathways of miRNA-21, along with the proteins and genes implicated in tumorigenesis, metastasis, therapy resistance to established treatments, and their significance in the diagnosis and prognosis of lung cancer. A total of 3294 articles were identified, and 37 papers were selected to compose the review, after analysing selection criteria. Of these, 57 % studies presented in vitro evaluation, 22 % studies showed in vivo analysis, and 12 clinical trials were found. This study elucidates the principal signaling pathways influenced by miRNA-21, which play a pivotal role in lung cancer development. This comprehensive review sheds light on the potential significance of miRNA-21 as a critical mechanism for improving the prognosis of lung cancer patients, facilitating the transition of experimental data into the clinical phase. Therefore, we summarized published articles of miRNA-21 modulated signal pathways in lung cancer.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155601"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The combination of p16 and Rb expression pattern is helpful to predict high-risk HPV infection and the primary site in lymph node metastases of squamous cell carcinoma","authors":"Ryosuke Kuga , Hidetaka Yamamoto , Fumiya Narutomi , Misa Suzuki , Rina Jiromaru , Takahiro Hongo , Kazuhisa Hachisuga , Nobuko Yasutake , Kiyoko Kato , Takashi Nakagawa , Yoshinao Oda","doi":"10.1016/j.prp.2024.155642","DOIUrl":"10.1016/j.prp.2024.155642","url":null,"abstract":"<div><div>Identifying the primary site of metastatic squamous cell carcinoma in lymph nodes can be challenging. An immunohistochemistry (IHC) analysis recently revealed that high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) typically show overexpression of p16 protein and a partial loss pattern of Rb. Nevertheless, the status of these markers in metastatic lesions is still unclear. In this study, we examined p16 and Rb expression status by IHC and transcriptionally active HR-HPV infection by mRNA <em>in situ</em> hybridization in paired primary and metastatic SCC lesions. A total of 50 patients with OPSCCs (n=17), hypopharyngeal SCCs (n=16), laryngeal SCCs (n=6), or uterine cervical SCCs (n=11) were enrolled. HR-HPV and p16 were positive in 21/50 (42 %) and 23/50 (46 %) patients, respectively. Primary and metastatic lesions showed concordant results for those three markers in individual patients. Among the p16-positive patients (n=23), HPV-positive cases typically showed a partial loss of Rb (n=20) and, rarely, a complete loss of Rb (n=1), whereas HPV-negative cases showed preserved Rb expression (n=2). All 27 p16-negative cases lacked HPV infection, while preserved expression and complete loss of Rb were observed in 26 and 1 of the p16-negative cases, respectively. Compared to standalone p16, the combination of p16 overexpression and Rb-partial/complete loss showed equally excellent sensitivity and negative predictive value (each 100 %) as well as improved specificity (100 % versus 93.1 %) and positive predictive value (100 % versus 91.3 %). Our results suggest that combining p16 and Rb expression patterns may be helpful in screening for HR-HPV infection in metastatic lymph nodes and in estimating the primary site of SCC.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155642"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ferroptosis as a hero against oral cancer","authors":"Varshini Vijayarangam , Mangayer karasi Gopalakrishnan Deviparasakthi , Priyanka Balasubramanian , Thirunavukkarasu Palaniyandi , Rekha Ravindran , Muath Suliman , Mohd Saeed , Sudhakar Natarajan , Asha Sivaji , Gomathy Baskar","doi":"10.1016/j.prp.2024.155637","DOIUrl":"10.1016/j.prp.2024.155637","url":null,"abstract":"<div><div>Cancer is an abnormal condition altering the cells to proliferate out of control simultaneously being susceptible to evolution. The lining which is made up of tissues in the lips, upper throat and mouth can undergo mutations, is recognised as mouth cancer or oral cancer. Substantial number of mouth lesions are identified at a point where it is typically not possible to get effective remedial care. Ferroptosis is a cutting-edge instance of cellular destruction which stands out in distinction to other sorts of cell death. It appears to have distinctive cellular, molecular and gene-level attributes and scavenges on deposits of reactive oxygen species triggered via iron-induced lipid peroxidation. It is said to be involved dichotomously in cancer development. Because the ferroptotic tumour cells put out numerous chemicals that alternatively signal for cancer attenuation or growth. There is increasing proof that researchers are now keenly investigating to stimulate ferroptosis through various inducers and pathways in the intent for oral cancer therapeutics, specifically to kill malignant tumours that refuse to respond well to conventional treatments. Also, it has the ability to reverse chemotherapy and radiotherapy resistance in victims maximising the success rate of the treatments. This review centres on the stimulation of ferroptosis as a stand-alone therapy for oral cancer, or in combination with other medicines, agents and pathways.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155637"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-coding RNAs as therapeutic targets in Parkinson’s Disease: A focus on dopamine","authors":"Khalid Saad Alharbi","doi":"10.1016/j.prp.2024.155641","DOIUrl":"10.1016/j.prp.2024.155641","url":null,"abstract":"<div><div>Parkinson’s Disease is a highly complicated neurological disorder, with a key manifestation of loss of dopaminergic neurons. Despite the plethora of medicines that alleviate the symptoms, there is an urgent need for new treatments acting on the fundamental pathology of PD. Non-coding RNAs are becoming increasingly important in gene regulation and various cellular processes and are found to play a role in PD pathophysiology. This review analyzes the cross-talk of distinct ncRNAs with dopamine signaling. We attempt to constrain the various ncRNA networks that can activate dopamine production. First, we describe the deregulation of miRNAs that target dopamine receptors and have been implicated in PD. Next, we turn to the functions of lncRNAs in dopaminergic neurons and the connections to susceptibility genes for PD. Finally, we will analyze the novel circRNAs, such as ciRS-7, which may modulate dopamine-linked processes and serve as possible PD biomarkers. In this review, we describe recent progress in dopamine neuron revival to treat PD and the therapeutic potential of ncRNA. This review critically evaluates the available data, and we predict the role of some ncRNAs, such as PTBP1, to become candidate treatment targets in the future. Thus, this review aims to summarize the molecular causes for the deficit in dopamine signaling in PD and point to novel ncRNAs-linked therapeutic directions in neuroscience.</div></div>","PeriodicalId":19916,"journal":{"name":"Pathology, research and practice","volume":"263 ","pages":"Article 155641"},"PeriodicalIF":2.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}