Hassan Zaman, Aakif Khan, Khalid Khan, Shazma Toheed, Muhammad Abdullah, Hafiz Muhammad Zeeshan, Abdul Hameed, Muhammad Umar, Muhammad Shahid, Kausar Malik, Samia Afzal
{"title":"Adeno-Associated Virus-Mediated Gene Therapy.","authors":"Hassan Zaman, Aakif Khan, Khalid Khan, Shazma Toheed, Muhammad Abdullah, Hafiz Muhammad Zeeshan, Abdul Hameed, Muhammad Umar, Muhammad Shahid, Kausar Malik, Samia Afzal","doi":"10.1615/CritRevEukaryotGeneExpr.2023048135","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2023048135","url":null,"abstract":"<p><p>Choice of vector is the most critical step in gene therapy. Adeno-associated viruses (AAV); third generation vectors, are getting much attention of scientists to be used as vehicles due to their non-pathogenicity, excellent safety profile, low immune responses, great efficiency to transduce non-dividing cells, large capacity to transfer genetic material and long-term expression of genetic payload. AAVs have multiple serotypes and each serotype shows tropism for a specific cell. Different serotypes are used to target liver, lungs, muscles, retina, heart, CNS, kidneys, etc. Furthermore, AAV based gene therapies have tremendous marketing applications that can be perfectly incorporated in the anticipated sites of the host target genome resulting in life long expression of transgenes. Some therapeutic products use AAV vectors that are used to treat lipoprotein lipase deficiency (LPLD) and it is injected intramuscularly, to treat mutated retinal pigment epithelium RPE65 (RPE65) that is introduced to subretinal space, an intravenous infusion to treat spinal muscular atrophy and rAAV2-CFTR vector is introduced into nasal epithelial cells to treat cystic fibrosis. AAV therapies and other such interdisciplinary methodologies can create the miracles for the generation of precision gene therapies for the treatment of most serious and sometimes fatal disorders.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 6","pages":"87-100"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889276","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":"lncRNA EGFEM1P Drives the Progression of Papillary Thyroid Cancer by Regulating miR-6867-5p/CHI3L1 Axis.","authors":"Zhanwu Ma, Guoxian Wang, Lin Hu","doi":"10.1615/CritRevEukaryotGeneExpr.2023047995","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023047995","url":null,"abstract":"<p><p>Long noncoding RNA (lncRNA), a subgroup of noncoding RNA with > 200 nt, plays critical roles in cancer progression. Here, we aimed to explore the detailed biological function of lncRNA EGFEM1P during papillary thyroid cancer (PTC) progression. RT-qPCR and Western blot were used to analyze the expression of lncRNA EGFEM1P, miR-6867-5p, and CHI3L1. CCK8, colony formation, and Transwell migration assays were undertaken to assess PTC cell proliferation and migration. A xenograft tumor mouse model was also used to establish tumor growth in vivo. Luciferase reporter and anti-AGO2 RNA immunoprecipitation (RIP) assays were used to clarify the interplay between miR-6867-5p and lncRNA EGFEM1P or CHI3L1. We found lncRNA EGFEM1P and CHI3L1 to be highly expressed in PTC tissues and cells, while miR-6867-5p expression decreases. Functionally, lncRNA EGFEM1P silence delays PTC cell proliferation and migration, and impairs tumorigenesis in vivo. LncRNA EGFEM1P targets miR-6867-5p, and CHI3L1 is a target gene of miR-6867-5p. LncRNA EGFEM1P silence decreases the pro-proliferation and pro-migration caused by the miR-6867-5p inhibitor in PTC cells, and CHI3L1 silence abrogates the pro-tumorigenic action resulting from the miR-6867-5p inhibitor in PTC cells. Our data showed that lncRNA EGFEM1P targeting of the miR-6867-5p/CHI3L1 axis drives PTC progression, suggesting lncRNA EGFEM1P as a therapeutically target for PTC.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 6","pages":"29-41"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889277","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":"Changes of Oral Flora, Inflammatory Factors, and Immune Function Indicators in Patients with Chronic Periodontitis and Their Clinical Significance.","authors":"Guodong Jia, Zhenhu Ren","doi":"10.1615/CritRevEukaryotGeneExpr.2023048819","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023048819","url":null,"abstract":"<p><p>This research focuses on investigating the changes of oral flora, inflammatory factors, and immune function indicators in patients with chronic periodontitis (CP) and their clinical significances. Clinical indices such as gingival index (GI) and sulcus bleeding index (SBI) of the study subjects were recorded. The levels of oral flora, inflammatory factors and T lymphocyte subsets in gingival crevicular fluid (GCF) of the study subjects were measured. To analyze the correlation between GI and gingival SBI and oral flora, inflammatory factors, and immune function indicators, Pearson correlation analysis was performed. Porphyromonas gingivalis, Streptococcus digestiveis, Prevotella intermedia, Veronococcus, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, CD3+, CD4+, and CD4+/CD8+ had a positive correlation with GI and SBI, while IL-10 and CD8+ were negatively correlated with GI and SBI. Oral flora, inflammatory factors and immune function indicators levels are largely elevated in patients with CP and they are correlated with CP clinical indicators.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 7","pages":"57-64"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10050267","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":"N6-Methyladenosine Modification and Prognostic Analysis of UBE2K in Hepatocellular Carcinoma: A Potential Target.","authors":"Jinhui Guo, Jie Zhao","doi":"10.1615/CritRevEukaryotGeneExpr.2023048801","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023048801","url":null,"abstract":"<p><p>The treatment of hepatocellular carcinoma (HCC) is still relatively lacking, the prognosis is poor, and the potential mechanism of carcinogenesis has not been thoroughly studied. In this study, Ubiquitin-conjugating enzyme E2K (UBE2K) transcript levels in HCC patients were up-regulated in two databases, GEO and TCGA. External validation was performed using Western blot experiments. Compared to normal liver cells, UBE2K was upregulated in HCC cell lines. The survival curve and prognosis model revealed that the expression of UBE2K was of high prognostic value in patients with HCC. Transwell assay, wound healing assay and sphere formation assay were used to evaluate the effects of knockdown and overexpression of UBE2K on HCC cells. Overexpression of UBE2K promoted the invasion, migration and stemness of HCC cells, while knocking down UBE2K attenuated the invasion, migration and stemness of HCC cells. Then, through a series of functional analysis (GO and KEEG), it was found that UBE2K played an important role in mRNA processing. We speculate that UBE2K may be involved in HCC progression through its own N6-methyladenosine modification. We therefore used a global methylation inhibitor (3-deazaadenosine) to treat HCC cells and found a gradient increase in the mRNA level of UBE2K. Collectively, the results suggest that UBE2K may be a promising molecular target for the treatment of HCC.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 8","pages":"41-55"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053244","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":"System Analysis Based on Pancreatic Cancer Progression Identifies BRINP2 as a Novel Prognostic Biomarker.","authors":"Yixing Kang, Xiangwen Xu, Jikui Liu","doi":"10.1615/CritRevEukaryotGeneExpr.2023048337","DOIUrl":"10.1615/CritRevEukaryotGeneExpr.2023048337","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system, which develops rapidly and has no obvious early symptoms. This study aims to discover the biomarkers associated with PAAD development. We obtained RNA expression of PAAD patient samples and corresponding clinical data from The cancer genome atlas (TCGA), and screened out BMP/RA-inducible neural-specific protein 2 (BRINP2) gene which is highly associated with PAAD severity. Then, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and single-sample gene set enrichment analysis (ssGSEA) analysis were performed to explore the biological functions of BRINP2. Subsequently, long non-coding RNA (lncRNAs) associated with BRINP2 were screened out via correlation analysis, and Cox regression analysis and least absolute shrinkage selection operator (LASSO) regression analysis were used to construct the risk prediction model. We further validated the expression level of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in vitro. We proposed that BRINP2 might be correlated to the tumor immune microenvironment and could also be used as a biomarker for PAAD progression. GO enrichment analysis and KEGG pathway analysis showed that the prognostic model was highly correlated to immune microenvironment-related pathways. Additionally, we established a BRINP2-associated lncRNAs prognostic model consisting of three lncRNAs. We validated the expression trends of BRINP2 and its associated lncRNAs in BRINP2-associated lncRNAs prognostic model in PAAD cells with various severity of metastatic potential using the quantitative real-time PCR (qRT-PCR). Meanwhile, pRRophetic R package was employed to predict potential therapeutic drugs for BRINP2-associated lncRNAs prognostic model of PAAD. The results suggest that BRINP2 can be used as a novel prognostic biomarker for PAAD.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 7","pages":"1-16"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425359","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":"Exosome-Mediated lncRNA LINC01140 Attenuates Breast Cancer Progression by Regulating the Wnt/β-Catenin Pathway.","authors":"Zhe Guo, Yang Li, Wenhuan Li, Hai Li, Zhiyong Wu","doi":"10.1615/CritRevEukaryotGeneExpr.2023048344","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023048344","url":null,"abstract":"<p><p>Exosome-delivered long non-coding RNAs have a role in the cancer control. It is unknown how exosomal LINC01140 contributes to the breast cancer (BC) growth. The purpose of this investigation is to identify exosomal LINC01140's function in the development of breast cancer. Using quantitative reverse transcripion polymerase chain reaction, the expression of LINC01140 was measured. To investigate how LINC01140 overexpression impacts BC cell proliferation, CCK-8 as well as colony formation assays (CFA) were employed. The expression of apoptosis-related proteins (Bax and Bcl-2) and Wnt/β-catenin signal pathway-related proteins (Wnt, C-myc, β-catenin, and p-GSK-3β) was assessed through Western blotting. Exosomes from BC cells were verified by western blotting to measure CD63 and CD9 levels. To examine how exosomal LINC01140 affects Wnt/β-catenin signaling pathway and xenograft tumor in nude mice, BC cell exosomes that were overexpressing LINC01140 were obtained and co-cultured with BC cells. In BC, it was discovered that LINC01140 had poor expression. BC cell proliferation was inhibited by overexpressing LINC01140, and the levels of the proteins Bcl-2, β-catenin, C-myc, and Wnt were lowered while Bax and p-GSK-3 were increased. In addition, exosomal LINC01140 hindered the activation of the Wnt/β-catenin signaling pathway, leading to a decrease in the growth of breast cancer cells in vivo. The presence of exosomal LINC01140 impedes the initiation of Wnt/β-catenin and reduces the cancerous characteristics of BC cells.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 7","pages":"31-42"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425362","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}
Xiao Zuo, Yan Shao, Yuhang Liang, Chenglong Huo, Shuai Wang
{"title":"MIR222HG/LIN28B/ATG5 axis drives M2 macrophage polarization and proliferation of hepatocellular carcinoma cells","authors":"Xiao Zuo, Yan Shao, Yuhang Liang, Chenglong Huo, Shuai Wang","doi":"10.1615/critreveukaryotgeneexpr.2023049637","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2023049637","url":null,"abstract":"Long non-coding RNAs (lncRNAs) are involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aimed to investigated the potentials of MIR222HG in HCC. HCC cells were co-cultured with U937 cells. Gene expression was determined using RT-qPCR and western blot. Functional analysis was performed using CCK-8, colony formation, and flow cytometry assays. We found that MIR222HG was overexpressed in HCC patients as well as HepG2 and Huh7 cells. Overexpressed MIR222HG promoted tumor cell autophagy and the activation of M2-like tumor-associated macrophages (TAM2). Moreover, MIR222HG-mediated the activation of TAM2 drove the proliferation of HCC cells. Additionally, MIR222HG increased the mRNA expression as well as promoted the mRNA stability of ATG5 via binding to LIN28B. In conclusion, MIR222HG-mediated autophagy and the activation of TAM2 promote the aggressiveness of HCC cells via regulating LIN28B/ATG5 signaling.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"74 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134882313","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}
Li-Hong Gan, Ling Yao, Jin-Hua Yan, Ya-Qin Huang, Li Zheng, Peng Liu, Ling Lei
{"title":"Differential expression of KIF18B in gastric cancer and its role in chemotherapy sensitivity","authors":"Li-Hong Gan, Ling Yao, Jin-Hua Yan, Ya-Qin Huang, Li Zheng, Peng Liu, Ling Lei","doi":"10.1615/critreveukaryotgeneexpr.2023049523","DOIUrl":"https://doi.org/10.1615/critreveukaryotgeneexpr.2023049523","url":null,"abstract":"","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134883435","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":"Sympathetic Activation Promotes Cardiomyocyte Apoptosis in a Rabbit Susceptibility Model of Hyperthyroidism-Induced Atrial Fibrillation via the p38 MAPK Signaling Pathway.","authors":"Jialin Zheng, Shijian Zhao, Qishi Yang, Yantao Wei, Jianmei Li, Tao Guo","doi":"10.1615/CritRevEukaryotGeneExpr.2023046625","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023046625","url":null,"abstract":"<p><p>Excess thyroid hormone secretion can cause endocrine metabolic disorders, which can lead to cardiovascular diseases, including heart enlargement, atrial fibrillation (AF), and heart failure. The present study investigated the molecular mechanisms of hyperthyroidism-induced AF. A rabbit susceptibility model of hyperthyroidism-induced AF was constructed, and metoprolol treatment was administered. Norepinephrine levels were determined using enzyme-linked immunosorbent assay; quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to detect the expression of markers for sympathetic remodeling (growth associated protein 43 and tyrosine hydroxylase in atrial myocardial tissues and stellate ganglia). Primary rabbit cardiomyocytes were cultured and identified by immunofluorescence staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to measure cardiomyocyte apoptosis; western blot was used to detect the expression of apoptosis-related proteins, including Bax, Bcl-2, and cleaved caspase-3, as well as to measure the phosphorylation states of p38 mitogen-activated protein kinase (MAPK) pathway proteins. Metoprolol inhibited sympathetic activation and cardiomyocyte apoptosis in the rabbit model by inhibiting the p38 MAPK signaling pathway. Immunofluorescence staining results revealed that the rabbit cardiomyocytes were isolated successfully. Inhibition of p38 MAPK signaling alleviated norepinephrine-induced apoptosis in cardiomyocytes. Sympathetic activation promotes apoptosis in cardiomyocytes with hyperthyroidism-induced AF via the p38 MAPK signaling pathway. The results of the present study provide a novel theoretical basis for the potential clinical treatment of patients with hyperthyroidism and AF.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 5","pages":"17-27"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856843","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}
Man Li, Jianmin Zeng, Yuhuan Chang, Lili Lv, Guoliu Ye
{"title":"CCT3 as a Diagnostic and Prognostic Biomarker in Cervical Cancer.","authors":"Man Li, Jianmin Zeng, Yuhuan Chang, Lili Lv, Guoliu Ye","doi":"10.1615/CritRevEukaryotGeneExpr.2023048208","DOIUrl":"https://doi.org/10.1615/CritRevEukaryotGeneExpr.2023048208","url":null,"abstract":"<p><p>The chaperonin-containing TCP1 complex subunit 3 (CCT3) has been reported to be involved in the development and prognosis of many tumors, including cervical cancer (CC). This study aimed to analyze the expression and prognostic value of CCT3 in CC by bioinformatics and retrospective study. CCT3 gene expression profiles and clinical information in CC were downloaded from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. CCT3 expression was verified by quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry (IHC). Logistic regression and chi-square testing were used to analyze the relationship between CCT3 expression and the clinical characteristics of CC. Kaplan-Meier and Cox analyses were used to evaluate whether CCT3 affects the prognosis of CC. Nomogram and calibration curves were used to test the predictive value of CCT3. The expression of CCT3 in CC tissues was significantly upregulated compared with that in adjacent benign tissues, and was related to HPV16/18 infection, grade, and positive lymph nodes. High expression of CCT3 is associated with poor prognosis of CC and can be used as an independent risk factor for CC. The prognostic model based on CCT3 and CC clinical features has good predictive ability. CCT3 is overexpressed in CC, which is related to poor prognosis and expected to become a biomarker for CC.</p>","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":"33 6","pages":"17-28"},"PeriodicalIF":1.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343709","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}