Cytojournal最新文献

{"title":"Crispr-Cas9-based long non-coding RNA interference and activation identified that the aberrant expression of Myc-regulated ST8SIA6 antisense RNA 1 promotes tumorigenesis and metastasis in hepatocellular carcinoma.","authors":"Xueqian Liu, Dong Jiang, Yang Liu, Kun Xie, Yijun Zhao, Fubao Liu","doi":"10.25259/Cytojournal_109_2024","DOIUrl":"10.25259/Cytojournal_109_2024","url":null,"abstract":"<p><strong>Objective: </strong>Long non-coding RNAs (lncRNAs) participate in the formation, progression, and metastasis of cancer. This study aimed to explore the roles of the lncRNA ST8SIA6 antisense RNA 1 (ST8SIA6-AS1) in tumorigenesis and elucidate the underlying molecular mechanism of its upregulation in hepatocellular carcinoma (HCC).</p><p><strong>Material and methods: </strong>A total of 56 in-house pairs of HCC tissues were examined, and ST8SIA6-AS1 levels were determined through real-time polymerase chain reaction (PCR). The biological behavior of ST8SIA6-AS1 by Crispr-Cas9-based gene repression and activation was determined <i>in vitro</i> and <i>in vivo</i>. The binding sites and biological behavior of Myc proto-oncogene and forkhead box A on chromatin were investigated through luciferase reporter assays, chromatin immunoprecipitation-quantitative PCR, and co-immunoprecipitation (co-IP) assays. The regulatory mechanisms of ST8SIA6-AS1 expression were analyzed with encyclopedia of DNA elements and gene expression profiling interactive analysis.</p><p><strong>Results: </strong>The expression of ST8SIA6-AS1 significantly increased in multiple HCC cell lines and the 56 in-house pairs of HCC tissues (<i>P</i> = 0.0018). Functionally, high-efficiency Crispr-Cas9-based knockdown of ST8SIA6-AS1 revealed that ST8SIA6-AS1 knockdown attenuated the proliferation, migration, and infiltration of HCC cells and considerably reduced the growth rate of subcutaneous and orthotopic HCC tumors. Conversely, ST8SIA6-AS1 overexpression considerably improved the oncogenic characteristics of the HCC cells. Furthermore, ST8SIA6-AS1 upregulation was regulated by the direct binding of transcription factor Myc to the -260 bp to+155 bp and +1003 bp to +1312 bp regions of the ST8SIA6-AS1 transcription start site, which is a segment with high level of H3K27 acetylation. Myc knockdown or treatment with the BET bromodomain inhibitor JQ-1 considerably reduced ST8SIA6-AS1 RNA expression in the HCC cells.</p><p><strong>Conclusion: </strong>Our study has established the oncogenic role of ST8SIA6-AS1 and elucidated the Myc-dependent upregulation mechanism of ST8SIA6-AS1 in HCC, providing a profound theoretical molecular basis for the carcinogenic function of ST8SIA6-AS1 in HCC.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"53"},"PeriodicalIF":2.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal stromal tumor mimicking perineurioma: A case report.","authors":"Yu Pan, Yuan Gao, Ping Yang, Guohua Yu","doi":"10.25259/Cytojournal_104_2024","DOIUrl":"10.25259/Cytojournal_104_2024","url":null,"abstract":"<p><p>Although gastrointestinal stromal tumor (GIST) can present with various histological characteristics, GIST mimicking perineurioma has not been previously reported. We present the case of a 47-year-old woman diagnosed with GIST after laparoscopic resection of a stomach tumor near the lesser curvature of the gastric body close to the cardia. Morphological features resembled a perineurioma. c.1504_1509 (p.A502_Y503) duplication was found in exon 9 of kinase insert domain receptor (c-KIT). This specific mutation is associated with constitutive activation of the c-KIT, which is crucial in the pathogenesis of GIST. Such unique histological characteristics broaden our understanding of the morphological diversity within GISTs and underscore the importance of considering an extended differential diagnosis when encountering atypical gastrointestinal tumors. This rare presentation may challenge conventional diagnostic criteria and could influence therapeutic strategies, emphasizing the need for comprehensive histological and molecular assessments in patient management.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"51"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the anti-cancer potential of sulfatase 1 and its underlying mechanism in non-small cell lung cancer.","authors":"Bingling Zhang, Daping Luo, Lan Xiang, Jun Chen, Ting Fang","doi":"10.25259/Cytojournal_71_2024","DOIUrl":"10.25259/Cytojournal_71_2024","url":null,"abstract":"<p><strong>Objective: </strong>Patients with non-small cell lung cancer (NSCLC) have poor prognoses. Sulfatase 1 (SULF1) is an extracellular neutral sulfatase and is involved in multiple physiological processes. Hence, this study investigated the function and possible mechanisms of SULF1 in NSCLC.</p><p><strong>Material and methods: </strong>Difference in SULF1 expression level between tumors and normal lung tissues was analyzed through bioinformatics and clinical sampling, and the effects of SULF1 expression on prognosis were investigated through Kaplan-Meier analysis. SULF1 level in NSCLC cells was modulated through small interfering ribonucleic acid interference. NSC228155, which is an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway agonist, was for handling NSCLC cells. SULF1 expression level was tested through quantitative reverse transcriptase real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated with cell counting kit-8, 5-ethynyl-2-deoxyuridine, and transwell assays, and the levels of epithelial-to-mesenchymal transition (EMT)- and EGFR/MAPK pathway-related proteins were detected through Western blot.</p><p><strong>Results: </strong>Bioinformatics and clinical samples showed that NSCLC tumor tissues had elevated SULF1 expression levels relative to those of normal tissues (<i>P</i> < 0.05). Patients with NSCLC and high SULF1 expression levels experienced poorer prognosis than those of low SULF1 expression levels (<i>P</i> < 0.05). SULF1 knockdown repressed the malignant biological behavior, including proliferation, migration, and invasion, of the NSCLC cells (<i>P</i> < 0.05). Mechanistically, SULF1 knockdown augmented E-cadherin level and abated N-cadherin and vimentin protein levels (<i>P</i> < 0.05). These results confirmed that EMT was inhibited. In addition, the knockdown of SULF1 reduced the phosphorylation of EGFR, extracellular signal-regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and NSC228155 partially reversed these changes, which were affected by SULF1 knockdown. Meanwhile, NSC228155 partially reversed the inhibition of EMT, migration, and invasion affected by SULF1 knockdown.</p><p><strong>Conclusion: </strong>SULF1 knockdown inhibits the proliferation, migration, invasion, and EMT of NSCLC cells by inactivating EGFR/MAPK pathway.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"52"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin superfamily member 1 upregulates myc proto-oncogene to accelerate invasion and metastasis of endometrial cancer: Molecular mechanisms and therapeutic prospects.","authors":"Jing Wei, Jinxiang Jiang, Shuhong Zhang, Shuai Dong","doi":"10.25259/Cytojournal_81_2024","DOIUrl":"10.25259/Cytojournal_81_2024","url":null,"abstract":"<p><strong>Objective: </strong>Endometrial cancer (EC) is a common gynecological malignancy, and its metastasis is one of the primary causes of treatment failure. Immunoglobulin superfamily member 1 (IGSF1), a membrane protein, has been associated with the aggressiveness and metastatic capability of various cancers. However, the role and mechanism of this protein in EC remains unclear. Therefore, this study aimed to explore the role of IGSF1 in EC and its possible mechanism.</p><p><strong>Material and methods: </strong>In this study, IGSF1 expression was knocked down through small interfering RNA and short hairpin RNA techniques, and its levels were controlled through overexpression experiments to observe its effects on Ishikawa cells. Wound healing assays, Transwell migration and invasion assays, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence double labeling were performed to evaluate the ability of cells to migrate, invade, and express markers of the epithelium mesenchymal transition (EMT). In addition, we investigated the regulatory role of IGSF1 in Myc proto-oncogene (c-Myc) expression and its function in lung metastasis through animal models of lung metastasis.</p><p><strong>Results: </strong>The results indicate that IGSF1 knockdown inhibited EMT and greatly reduced the invasion ability of Ishikawa cells (<i>P</i> < 0.01). Animal experiments demonstrated that IGSF1 knockdown reduced the number of pulmonary metastatic foci (<i>P</i> < 0.001). On the other hand, IGSF1 overexpression increased Ishikawa cells' ability to migrate and invade (<i>P</i> < 0.01). IGSF1 overexpression also inhibited E-cadherin expression and promoted that of vimentin (<i>P</i> < 0.001). The expression of c-Myc decreased following IGSF1 knockdown and increased after its overexpression. Silencing of c-Myc reversed the oncogenic effects of IGSF1 (<i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>IGSF1 promotes EMT and metastasis in EC through the upregulation of the c-Myc expression. IGSF1 may serve as a potential therapeutic target for EC, and its inhibition can offer new strategies for mitigating the aggressiveness and metastatic potential of this malignancy.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"49"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of lysine-specific histone demethylase 1A suppresses adenomyosis through reduction in ectopic endometrial stromal cell proliferation, migration, and invasion.","authors":"Limei Cui, Changmei Sang, Ruoqing Li, Shuping Zhao","doi":"10.25259/Cytojournal_48_2024","DOIUrl":"10.25259/Cytojournal_48_2024","url":null,"abstract":"<p><strong>Objective: </strong>Deep endometriosis is now referred to as adenomyosis externa, whereas adenomyosis is once known as endometriosis interna. Lysine-specific histone demethylase 1A (KDM1A, commonly LSD1) is a lysine demethylase that targets histone and non-histone proteins. This study aimed to assess how KDM1A affects the migration, invasion, and proliferation of adenomyosis-derived endometrial stromal cells (ESCs).</p><p><strong>Material and methods: </strong>Immunocytochemistry staining was used to identify primary ectopic endometrial stromal cells (EESCs) and eutopic endometrial stromal cells (EuESCs) were isolated and purified from patients with complete hysterectomy for adenomyosis. Cell counting kit-8 assay, colony formation, wound scratch, and transwell assays were used to investigate the effect of silencing KDM1A on the inhibition cell viability, colony, migration, and invasion, respectively. Mechanistic investigations were carried out by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Vimentin staining was highly positive and cytokeratin staining was nearly negative in EESCs and EuESCs. KDM1A silencing reduced the ability of EESCs and EuESCs to proliferate (<i>P</i> < 0.001). The proliferation, motility, and invasiveness of EESCs and EuESCs were markedly reduced when KDM1A was silenced (<i>P</i> < 0.001). KDM1A silencing substantially downregulated invasion- and migration-related proteins or genes according to Western blot and qRT-PCR analysis (<i>P</i> < 0.05). EESCs and EuESCs with KDM1A silencing showed a higher reduction in these proteins than the control group (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>In adenomyosis, silencing KDM1A can limit the motility, invasiveness, and proliferation of EuESCs and EESCs. These outcomes could potentially correlate with the decreased expression levels of matrix metalloproteinases (MMP)-2, MMP-9, Fascin, and Erzin proteins.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"50"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular classification of endometrial cancer: Impact on adjuvant treatment planning.","authors":"Dimitrios Zouzoulas, Dimitrios Tsolakidis, Iliana Sofianou, Panagiotis Tzitzis, Stavroula Pervana, Maria Topalidou, Eleni Timotheadou, Grigoris Grimbizis","doi":"10.25259/Cytojournal_37_2024","DOIUrl":"10.25259/Cytojournal_37_2024","url":null,"abstract":"<p><strong>Objective: </strong>The traditional histopathological analysis of endometrial cancer (EC) is the main risk group classification tool (low, intermediate, high-intermediate, and high) for the implementation of adjuvant treatment. The International Federation of Gynecology and Obstetrics staging system of EC has incorporated a new molecular classification that serves as a new triage tool for optimal treatment planning for these patients. Our study aimed to investigate the prognostic role of the new molecular classification in EC.</p><p><strong>Material and methods: </strong>A prospective study was conducted in the 1^st Department of Obstetrics and Gynecology from January 1, 2022, to March 30, 2024, and included all new EC cases that presented the multidisciplinary tumor (MDT) board after surgery. We considered the traditional pathologic analysis and new molecular classification after performing tests on microsatellite instability (MSI), DNA polymerase epsilon (POLE) mutation, and p53 immunohistochemistry testing.</p><p><strong>Results: </strong>The study included 65 patients with presumed early endometrial. All patients underwent surgery and subsequent molecular testing. Among the patients, 35 (54%) had a \"positive\" result in all of the three markers of molecular classification: 14 patients presented with MSI-H, 5 with POLE gene mutation, and 17 with p53 abnormal expression. One case of multiple classifiers was presented. After the integration of molecular classification, a change was observed in the final MDT board decision in 23 cases (35.4%), including six cases of overtreatment and 17 cases of undertreatment, with statistical significance (<i>P</i> = 0.03469).</p><p><strong>Conclusion: </strong>The data suggest that the new molecular classification, that is, testing for POLE mutation, MSI, and p53 mutation and for endometrial carcinoma, is a valuable tool for the recurrence risk prognosis and improved planning of adjuvant treatment for EC.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"47"},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision medicine for patients with salivary gland neoplasms: Determining the feasibility of implementing a next-generation sequencing-based RNA assay in a hospital laboratory.","authors":"Gloria Hopkins Sura, Jim Hsu, Dina R Mody, Jessica S Thomas","doi":"10.25259/Cytojournal_152_2024","DOIUrl":"10.25259/Cytojournal_152_2024","url":null,"abstract":"<p><strong>Objective: </strong>Diagnosing neoplasms of the salivary gland is challenging, as morphologic features of these tumors are complex, and well-defined diagnostic categories have overlapping features. Many salivary gland neoplasms are associated with recurrent genetic alterations. The utilization of RNA-based targeted next-generation sequencing (NGS) panels for the detection of cancer-driving translocations and mutations is emerging in the clinical laboratory. Our objective was to conduct a proof-of-concept study to show that in-house molecular testing of salivary gland tumors can enhance patient care by supporting morphologic diagnoses, thereby improving therapeutic strategies such as surgical options and targeted therapies.</p><p><strong>Material and methods: </strong>Residual formalin-fixed paraffin-embedded salivary gland neoplasm specimens from a cohort of 17 patients were analyzed with the Archer FusionPlex Pan Solid Tumor v2 panel by NGS on an Illumina NextSeq550 platform.</p><p><strong>Results: </strong>We identified structural gene rearrangements and single nucleotide variants in our patient samples that have both diagnostic and treatment-related significance. These alterations included <i>PLAG1, MAML</i>, and <i>MYB</i> fusions and <i>BRAF, CTNNB1, NRAS</i>, and <i>PIK3CA</i> mutations.</p><p><strong>Conclusion: </strong>Our RNA-based NGS assay successfully detected known gene translocations and mutations associated with salivary gland neoplasms. The genetic alterations detected in these tumors demonstrated potential diagnostic, prognostic, and therapeutic value. We suggest that incorporating in-house ancillary molecular testing could greatly enhance the accuracy of salivary gland fine needle aspiration cytology and small biopsies, thereby better guiding surgical decisions and the use of targeted therapies.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"48"},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of ribosomal protein L22-like 1 arrests the cell cycle and promotes apoptosis in colorectal cancer.","authors":"Chunming Li, Xinna Du, Hu Zhang, Shuang Liu","doi":"10.25259/Cytojournal_29_2024","DOIUrl":"10.25259/Cytojournal_29_2024","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Colorectal cancer (CRC) remains a remarkable challenge despite considerable advancements in its treatment, due to its high recurrence rate, metastasis, drug resistance, and heterogeneity. Molecular targets that can effectively inhibit CRC growth must be identified to address these challenges. Therefore, we aim to reveal the regulatory effect of ribosomal protein L22-like 1 (RPL22L1) on the proliferation and apoptosis of CRC cells and its potential mechanism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;We detected the expression of RPL22L1 from the Cancer Genome Atlas, Gene Expression Omnibus and UALCAN databases. The effects of RPL22L1 on CRC growth and migration were determined by knocking down RPL22L1 in human CRC cell lines and those on the cell cycle and apoptosis using flow cytometry. The influence of RPL22L1 knockdown on xenograft tumor growth was verified &lt;i&gt;in vivo&lt;/i&gt;. The potential &lt;i&gt;RPL22L1&lt;/i&gt; mechanisms in promoting cancer were predicted with RNA sequencing (RNAseq). The molecular mechanism of enhanced apoptosis and cell cycle arrest in RPL22L1 knockdown was revealed using real-time reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and Western blotting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The present study reveals a considerable upregulation of &lt;i&gt;RPL22L1&lt;/i&gt; expression in CRC as well as in diverse tumor tissues, and most cells within the CRC tumor microenvironment (TME) demonstrate &lt;i&gt;RPL22L1&lt;/i&gt; expression. Notably, this elevated expression level of &lt;i&gt;RPL22L1&lt;/i&gt; exhibits a strong association with an unfavorable prognosis among patients diagnosed with CRC (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Furthermore, the association between &lt;i&gt;RPL22L1&lt;/i&gt; expression and the CRC TME index did not exhibit statistical significance (&lt;i&gt;P&lt;/i&gt; &gt; 0.05). However, RPL22L1 knockdown experiments revealed a substantial suppression of growth and migratory capacities in CRC cells RKO and HCT116 (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Flow cytometry analysis exhibited that on &lt;i&gt;RPL22L1&lt;/i&gt; knockdown, a remarkable arrest of the G1 and S phases of the cell cycle (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) occurred. In addition, a remarkable elevation in the level of cell apoptosis was observed (&lt;i&gt;P&lt;/i&gt; &lt; 0.001). RNAseq exhibited that cell cycle, DNA replication, and mechanistic target of rapamycin (mTOR) complex 1pathway were inhibited after &lt;i&gt;RPL22L1&lt;/i&gt; knockdown, whereas the apoptosis pathway was activated (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Validation through RT-qPCR and western blot analysis also corroborated the downregulation of P70S6K, MCM3, MCM7, GADD45B, WEE1, and MKI67 expression levels, following &lt;i&gt;RPL22L1&lt;/i&gt; knockdown (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Consequent rescue experiments offered supportive evidence, indicating the involvement of the mTOR pathway in mediating the influence of RPL22L1 on the promotion of cell cycle progression. Moreover, &lt;i&gt;in vivo&lt;/i&gt; assays involving tumor-bearing mice exhibited that diminished RPL22L1 levels led to arrested CRC growth (&lt;i&gt;P&lt;/i&gt; &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"45"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogene 5'-3' exoribonuclease 2 enhances epidermal growth factor receptor signaling pathway to promote epithelial-mesenchymal transition and metastasis in non-small-cell lung cancer.","authors":"Yonghui Cheng, Mengge Wen, Xiaochun Wang, Hao Zhu","doi":"10.25259/Cytojournal_49_2024","DOIUrl":"10.25259/Cytojournal_49_2024","url":null,"abstract":"<p><strong>Objective: </strong>Epithelial-mesenchymal transition (EMT) and metastasis are the primary causes of mortality in non-small-cell lung cancer (NSCLC). 5'-3' exoribonuclease 2 (XRN2) plays an important role in the process of tumor EMT. Thus, this investigation mainly aimed to clarify the precise molecular pathways through which XRN2 contributes to EMT and metastasis in NSCLC.</p><p><strong>Material and methods: </strong>Western blot and quantitative real-time polymerase chain reaction were first used to assess XRN2 levels in NSCLC cells. Subsequently, short hairpin RNA-XRN2 (Sh-XRN2) and XRN2 overexpression (Ov-XRN2) plasmids were transfected to NSCLC cells. The effects of Sh-XRN2 and Ov-XRN2 on NSCLC cell migration and invasion were evaluated by Transwell assay. Western blot experiments were conducted to assess the effects of Sh-XRN2 and Ov-XRN2 on proteins related to EMT and the epidermal growth factor receptor (EGFR) signaling pathway in H460 cells. Then, Sh-XRN2 and EGFR overexpression (Ov-EGFR) plasmids were transfected to NSCLC cells. Changes in NSCLC cell migration and invasion were measured using a Transwell assay with Sh-XRN2 and Sh-XRN2+Ov-EGFR. Changes in the expression of proteins related to EMT in NSCLC cells were detected by Western blot assays with Sh-XRN2 and Sh-XRN2+Ov-EGFR. Furthermore, a subcutaneous tumor model for NSCLC was established. Immunohistochemical analysis was performed to assess the levels of Cluster of Differentiation 31 (CD31) in lung metastatic lesions. H460 cells transfected with Sh-XRN2, Ov-XRN2 or Sh-XRN2+Ov-EGFR were co-cultured with human umbilical vein endothelial cells (HUVECs) to assess the tube formation ability of the cells.</p><p><strong>Results: </strong>Compared with those observed in human bronchial epithelial cells (BEAS-2B cells), XRN2 expression levels were significantly upregulated in NSCLC cell lines (H460 cells) (<i>P</i> < 0.001). XRN2 overexpression considerably promoted the NSCLC cell migration and invasion, EMT process, and tube formation ability of HUVECs (<i>P</i> < 0.001). On the contrary, XRN2 knockdown led to a reduction in these processes. In addition, XRN2 overexpression increased the expression levels of CD31 in lung metastatic lesions and activated the phosphorylation of EGFR signaling pathway (<i>P</i> < 0.001). Furthermore, Sh-XRN2+Ov-EGFR significantly promoted migration, invasion, and EMT processes in H460 cells (<i>P</i> < 0.001). In the meantime, compared with the co-H460+Sh-XRN2+Ov-NC group, co-H460+Sh-XRN2+Ov-EGFR significantly enhanced the tube formation ability of HUVECs (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>XRN2 promoted EMT and metastasis in NSCLC through improving the phosphorylation of the EGFR signaling pathway in NSCLC cells.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"46"},"PeriodicalIF":2.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear receptor subfamily 4 group a member 1 eases angiotensin II-arose oxidative stress in vascular smooth muscle cell by boosting nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 3 transcription.","authors":"Li Shen, Feng Li, Ke Xia, Lingli Zhan, Dan Zhang, Zhiqiang Yan","doi":"10.25259/Cytojournal_86_2024","DOIUrl":"10.25259/Cytojournal_86_2024","url":null,"abstract":"<p><strong>Objective: </strong>Hypertension significantly contributes to morbidity and mortality. Nuclear receptor subfamily 4 group a member 1 (Nur77) participates in regulating oxidative stress, but the mechanism in hypertension remains unclear. This study aimed to explore the function of Nur77 in oxidative stress induced by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs) in hypertension.</p><p><strong>Material and methods: </strong>First, models of VSMC with Nur77, nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 3 (NLRC3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) knockdown or overexpression were constructed using Short Hairpin RNA (Nur77) or pcDNA3.1 vector, respectively. Next, the putative-binding motifs between Nur77 and NLRC3 promoters were detected by dual luciferase assay. We conducted reverse transcription quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis to detect Nur77, NLRC3, and TRAF6 levels in VSMCs. Then, cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and 2',7'-dichlorofluorescin diacetate were employed to examine the impact of the knockdown or overexpression of Nur77, NLRC3, and TRAF6 on VSMCs treated with Ang II. The assays measured cell viability and proliferation, cell migration, malondialdehyde levels, and reactive oxygen species levels.</p><p><strong>Results: </strong>The overexpression of Nur77 repressed cell growth (<i>P</i> < 0.001), migration (<i>P</i> < 0.01), and oxidative stress (<i>P</i> < 0.01) induced by Ang II in VSMCs. Nur77 transcriptionally promoted the expression of NLRC3 (<i>P</i> < 0.001), and the upregulation of NLRC3 suppressed cell proliferation (<i>P</i> < 0.05) and oxidative stress (<i>P</i> < 0.001) mediated by Ang II. Furthermore, NLRC3 negatively regulated the TRAF6/nuclear factor-kappa B (NF-κB) axis activated by Ang II, which resulted in the repression of hyperproliferation of VSMCs (<i>P</i> < 0.01) and oxidative stress (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>Nur77 suppressed growth and oxidative stress induced by Ang II in VSMCs by promoting NLRC3 transcription, which, further, repressed the TRAF6/NF-κB axis. This understanding provides novel insights into the pathogenesis of hypertension.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"21 ","pages":"43"},"PeriodicalIF":2.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}