{"title":"An anoikis-related gene signature predicts prognosis in patients with acute myeloid leukemia and immunotherapy.","authors":"Rong Xu, Ashuai Du, Jianbo Li, Qinglong Yang","doi":"10.62347/MJTA2660","DOIUrl":"10.62347/MJTA2660","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a malignant blood disorder and the most common type of acute leukemia in adults. Notwithstanding the plethora of therapeutic modalities, a significant cohort of patients fail to respond to treatment and experience relapse. Anoikis, a distinct modality of programmed cell death, has been linked to cancer progression. However, the prognostic significance of anoikis in AML remains unclear. In this study, a non-negative matrix factorization algorithm was utilized to efficiently reduce the dimensions of merged datasets. We used differential analysis, weighted gene co-expression network analysis (WGCNA), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to identify genes associated with prognosis and develop a risk scoring model. Immunohistochemistry was conducted to assess the expression levels of key genes in clinical samples. The association between risk score and the tumor microenvironment (TME), stemness, clinical characteristics, and immunotherapy was evaluated. We identified 41 AML anoikis-related genes (ANRGs) related to survival, and seven genes were chosen to develop prognostic models. The prognostic risk score combined with the clinical and pathological features of AML was used to develop a nomogram, and decision curve analysis demonstrated the net clinical benefit of the model. Furthermore, analysis of ANRGs revealed that PDGFRB inhibition significantly reduced the proliferation of AML cells, promoted apoptosis, and inhibited AML progression both in vitro and in vivo, indicating that PDGFRB plays a crucial role in AML development.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5116-5132"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Zhang, Siguang Xu, Dandan Li, Songxin Wu, Miaomiao Han, Yifei Han, Zixi Wang, Dan Qiao, Hang Yuan, Baoshun Du, Hongwei Chen, Zheying Zhang
{"title":"The small protein LINC01547-ORF inhibits colorectal cancer progression by regulating the CLDN18-FAK-AKT axis.","authors":"Shuai Zhang, Siguang Xu, Dandan Li, Songxin Wu, Miaomiao Han, Yifei Han, Zixi Wang, Dan Qiao, Hang Yuan, Baoshun Du, Hongwei Chen, Zheying Zhang","doi":"10.62347/PNKH7683","DOIUrl":"10.62347/PNKH7683","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA)-encoded small proteins play a major role in colorectal cancer. To identify more functional encoded small proteins, ribosome profiling data from colorectal cancer (CRC) cells were screened for ribosome-associated lncRNAs. The search identified LINC01547 that was shown to encode a small protein of 76 amino acids, termed LINC01547-ORF. Real-time quantitative fluorescence showed that LINC01547 expression was downregulated in colorectal cancer tissues. However, cell functional assays revealed that LINC01547 inhibited the proliferation and migration of colorectal cancer cell lines. Meanwhile, western blot and immunofluorescence assays confirmed that LINC01547 encoded LINC01547-ORF. Cellular functional assays indicated that compared with LINC01547 itself, LINC01547-ORF inhibited the proliferation and migration of colorectal cancer cell lines. Gene set enrichment analysis identified enrichment in the focal adhesion pathway and association with CLDN18 protein, whereas protein molecular docking models revealed interacting domains and amino acid residue sites. Of note, co-immunoprecipitation and immunofluorescence experiments showed that LINC01547-ORF could bind to the CLDN18 protein and that this interaction reduced CLDN18 ubiquitination, thereby promoting protein expression. Finally, western blot and immunofluorescence assays confirmed that LINC01547-ORF could target CLDN18 to inhibit the FAK/PI3K/AKT signaling pathway, suppressing colorectal cancer cell development. These findings suggest that the LINC01547-ORF-encoded small protein inhibits proliferation and migration in colorectal cancer, thereby offering a promising direction for treating this disease.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5504-5520"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wensi Zhao, Yuan Chen, Jiping Xiao, Ze Tang, Li Wang, Yiping Ren, Yongshun Chen
{"title":"Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer.","authors":"Wensi Zhao, Yuan Chen, Jiping Xiao, Ze Tang, Li Wang, Yiping Ren, Yongshun Chen","doi":"10.62347/XKUJ3012","DOIUrl":"10.62347/XKUJ3012","url":null,"abstract":"<p><p>Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; <i>P</i> = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5351-5364"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vu Pham Thao Vy, Jerry Chin-Wei Chien, Wiwan Irama, Hao-Yang Wu, Tzu-I Wu, Wei-Yu Chen, Chia-Hao Liang, Truong Nguyen Khanh Hung, Wilson T Lao, Wing P Chan
{"title":"Machine learning models using multiparametric MRI for preoperative risk stratification in endometrial cancer.","authors":"Vu Pham Thao Vy, Jerry Chin-Wei Chien, Wiwan Irama, Hao-Yang Wu, Tzu-I Wu, Wei-Yu Chen, Chia-Hao Liang, Truong Nguyen Khanh Hung, Wilson T Lao, Wing P Chan","doi":"10.62347/MALY3908","DOIUrl":"10.62347/MALY3908","url":null,"abstract":"<p><p>This study evaluated the efficacy of machine learning and radiomics of preoperative multiparameter MRIs in predicting low- vs high-risk histopathologic features and early vs advanced FIGO stage (IA vs IB or higher) in endometrial cancer. This retrospective study of patients with endometrial cancer histologically confirmed from 2008 through 2023 excluded those with: (a) previous treatment for endometrial carcinoma, (b) incomplete MRI examinations or low-quality MR images, (c) incomplete pathology reports, (d) non-visualized tumors on MRI, or (e) distant metastases. In total, 110 radiomic features were extracted using commercial PACS built-in software following segmentation after sagittal T2-weighted imaging (T2WI), contrast enhanced T1-weighted imaging (CE-T1WI), and diffusion weighted imaging (DWI). The radiomic features from each imaging sequence were utilized for initial modeling. A combined model, which included features retained from all 3 sequences, was then established. The area under the receiver operating characteristic curve (AUC) determined the efficacy of each model. For 5 specific histopathologic features, the combined model achieved AUCs of 0.87 (95% CI, 0.85-0.90), 0.90 (95% CI, 0.88-0.92), 0.88 (95% CI, 0.87-0.90), 0.88 (95% CI, 0.86-0.92), and 0.87 (95% CI, 0.86-0.90). This model incorporated 38 radiomic features: 12 from T2WI, 17 from CE-T1WI, and 9 from DWI. In conclusion, an MRI radiomics-based model can differentiate between early- and advanced-stage endometrial cancer and between low- and high-risk histologic markers, giving it the potential to predict high risk and stratify preoperative risk in those with endometrial cancer. The findings may aid personalized preoperative assessments to guide clinical decision-making in endometrial cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5400-5410"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning-based prognostic models and factors influencing the benefit of surgery on primary lesion for patients with lung cancer brain metastases.","authors":"Xixi Zhao, Chaofan Li, Mengjie Liu, Zeyao Feng, Xinyu Wei, Yusheng Wang, Jiaqi Zhao, Shuqun Zhang, Jingkun Qu","doi":"10.62347/PRFQ9244","DOIUrl":"10.62347/PRFQ9244","url":null,"abstract":"<p><p>Brain metastasis is very common in lung cancer and it's a fatal disease with extremely poor prognosis. Until now, there has been a lack of accurate and efficient prognostic models for patients with lung cancer brain metastases (LCBM), and the factors influencing the effectiveness of the surgery on primary lesion for these patients remain unclear. We used 7 machine learning algorithms to create prognostic models to predict the overall survival (OS) of LCBM based on the data from the Surveillance Epidemiology and End Results. Then, a series of validation methods, including area under the curve values, receiver operating characteristic curve analysis, calibration curves, decision curve analysis and external data validation were used to confirm the high discrimination, accuracy, and clinical applicability of the XGBoost models. Propensity score matching adjusted analysis was conducted for further stratified analysis to find factors influencing the benefit of surgery on primary lesion for LCBM. Models using XGBoost algorithm performed best. Surgery on primary lesion was a favorable independent prognostic factor for LCBM. Age > 70 years old, blacks, grade IV, stage T4, N3, other distant organ metastases, squamous cell carcinoma, large cell carcinoma and no radiation were all unfavorable factors of primary lung tumor surgery for the prognosis of LCBM. Our study is the first one to create highly accurate AI models to predict the OS of LCBM. Our in-depth stratified analysis found some influence factors of surgery on primary lesion for the prognosis of LCBM.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5154-5177"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quercetin suppresses cell viability in triple-negative breast cancer by targeting ORM2.","authors":"Xianhua Liu, Zhijun Chen","doi":"10.62347/DEPW1251","DOIUrl":"10.62347/DEPW1251","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is known for its aggressive nature, and Quercetin (QUE) has shown potential anti-cancer effects. In this study, we determined the IC50 of QUE for inhibiting cell viability in multiple TNBC, non-TNBC, and normal breast cell lines. We compared the expression of ORM2 in TNBC clinical samples and normal tissues. Additionally, we measured ORM2 expression in TNBC and normal breast cell lines. We determined the IC50 of QUE for inhibiting cell viability after ORM2 knockdown. An orthotopic implantation mice model was used to evaluate the treatment effect of QUE. We also conducted molecular docking and amino acid exchange validation to model the binding of QUE to ORM2. Furthermore, we performed a protein-protein interaction network analysis and GO enrichment analysis of differentially expressed genes associated with ORM2 in TNBC. QUE inhibited the viability of both TNBC and non-TNBC cell lines, but it was specifically associated with worse survival in TNBC patients. We observed higher expression of ORM2 in breast cancer cells compared to normal breast cells. Knockdown of ORM2 reduced the viability of TNBC cells. Treatment with QUE inhibited ORM2 expression and decreased viability in TNBC cells. In the animal model, QUE improved survival and downregulated ORM2 expression in tumors. Enrichment analysis provided insights into the potential functions of ORM2. Conclusion: Our findings indicate that QUE directly inhibits TNBC cell viability through its interaction with ORM2. These results contribute to our understanding of the anti-cancer mechanisms of QUE in TNBC and highlight ORM2 as a potential therapeutic target.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5269-5285"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hui-Ying Liu, Hao Lun Luo, Wen-Chin Lee, Yin Lun Chang, Yen-Ting Wu, Hung Jen Wang, Yao Chi Chuang, Yen Ta Chen, Lung-Chih Li, John L Gore, Chiang-Chi Huang
{"title":"Recurrence risk of erythropoiesis-stimulating agents on early-stage urothelial carcinoma in patients with end stage renal disease.","authors":"Hui-Ying Liu, Hao Lun Luo, Wen-Chin Lee, Yin Lun Chang, Yen-Ting Wu, Hung Jen Wang, Yao Chi Chuang, Yen Ta Chen, Lung-Chih Li, John L Gore, Chiang-Chi Huang","doi":"10.62347/UJAT9290","DOIUrl":"10.62347/UJAT9290","url":null,"abstract":"<p><p>Urothelial carcinoma (UC) predominantly arises in the bladder, but upper tract urothelial carcinomas (UTUCs) comprise 5-10% of cases. Patients with end-stage renal disease (ESRD) are at increased risk for UC, and erythropoiesis-stimulating agents (ESAs) are frequently used to manage anemia in ESRD. However, ESA use in cancer patients raises concerns about tumor progression and survival outcomes. This study aimed to assess the impact of ESA use on tumor recurrence, cancer-specific survival (CSS), and overall survival (OS) in patients with ESRD and early-stage UC. We analyzed data from the Chang-Gung Research Database (CGRD) in Taiwan, including 850 patients with ESRD and non-muscle-invasive bladder cancer (NMIBC) and 492 patients with ESRD and localized UTUC. The ESA group was compared to a non-ESA cohort, and inverse probability of treatment weighting (IPTW) was applied to minimize selection bias. Kaplan-Meier curves and log-rank tests were used to evaluate bladder recurrence-free survival, CSS, and OS. In NMIBC patients, ESA use did not significantly affect bladder recurrence-free survival, CSS, or OS. Similarly, ESA use in localized UTUC patients did not increase the risk of bladder recurrence or negatively impact CSS and OS. However, UTUC patients treated with ESA demonstrated a significantly increased risk of contralateral recurrence (P < 0.001). The use of ESA in patients with ESRD and early-stage UC appears safe regarding bladder recurrence, CSS, and OS, but clinicians should remain vigilant for contralateral recurrence in localized UTUC. These findings provide valuable insights into the complex management of anemia in patients with concurrent ESRD and UC, emphasizing the need for tailored clinical monitoring in this high-risk population.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5389-5399"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Dai, Ming-Gan Chen, Deng-Feng Zhu, Yi-Ting Cai, Ming Gao
{"title":"Risk factors of positive lymph node metastasis after radical gastrectomy for gastric cancer and construction of prediction models.","authors":"Gang Dai, Ming-Gan Chen, Deng-Feng Zhu, Yi-Ting Cai, Ming Gao","doi":"10.62347/PEDV7297","DOIUrl":"10.62347/PEDV7297","url":null,"abstract":"<p><p>Positive lymph node metastasis after radical gastrectomy for gastric cancer is a key factor affecting the prognosis of patients, and its mechanism is complex and multifactorial. The aim of this study is to identify the relevant risk factors for positive lymph node metastasis after radical gastrectomy for gastric cancer, and to construct corresponding predictive models. Through a retrospective analysis of clinical data of 316 gastric cancer patients who underwent radical surgery for gastric cancer, we found that age, maximum tumor diameter, degree of tumor differentiation, vascular invasion, depth of tumor infiltration, and CA199 were important factors affecting lymph node metastasis positivity in gastric cancer patients. Based on these factors, we constructed a Nomogram prediction model and found through internal validation that the model has good predictive performance. The area under the receiver operating characteristic curve (AUC) of the training and validation sets were 0.929 and 0.888, respectively. Clinical data of another 390 patients were collected for external verification. External validation results showed that the model had a predictive sensitivity of 75.76% (50/66), a specificity of 91.05% (295/324), and an accuracy of 88.46% (345/390). In addition, we also constructed a neural network prediction model and compared it with the Nomogram model. The results showed that the prediction performance of the Nomogram model was similar to that of the neural network model. The Nomogram model has been validated internally and externally, demonstrating high discrimination and accuracy, providing a convenient, intuitive, and personalized evaluation tool for clinicians, helping to optimize the postoperative management of gastric cancer patients and improve prognosis.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5216-5229"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqi He, Han Liu, Jianhua Cai, Sheng Shen, Jiwen Wang, Houbao Liu
{"title":"ASAP1 promotes extrahepatic cholangiocarcinoma progression by regulating the Wnt/β-catenin pathway in vitro and in vivo.","authors":"Jiaqi He, Han Liu, Jianhua Cai, Sheng Shen, Jiwen Wang, Houbao Liu","doi":"10.62347/RKQX3504","DOIUrl":"10.62347/RKQX3504","url":null,"abstract":"<p><p>This study sought to identify the relationship between ADP-ribosylation factor GTPase-activating protein (ASAP1) expression and clinical outcomes in extrahepatic cholangiocarcinoma (EHCC) patients. Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry were used to analyze the expression of ASAP1 in cholangiocarcinoma (CC) tissue samples and cell lines. The survival rate and clinicopathological characteristics of CC patients were also examined. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. Flow cytometry was used to assess the cell cycle distribution. Both <i>in vitro</i> and <i>in vivo</i> experiments showed that ASAP1 knockdown decreased cell proliferation, inhibited cell cycle progression, and increased apoptosis. ASAP1 regulates Wnt/β-catenin pathway activity in CC, promoting cell migration, and invasion in culture; and promotes tumor development <i>in vivo</i>. ASAP1 plays a key role in EHCC tumor development and could serve as a potential therapeutic target for EHCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5178-5192"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kai Lu, Wanchao Zhang, Xiaoqiang Tang, Ruohan Yin, Tao Wang, Xiaoyu Wei, Changjie Pan
{"title":"Mechanism of miR-503-5p on cardiac hemangioma and clinical validation.","authors":"Kai Lu, Wanchao Zhang, Xiaoqiang Tang, Ruohan Yin, Tao Wang, Xiaoyu Wei, Changjie Pan","doi":"10.62347/EVMG4299","DOIUrl":"10.62347/EVMG4299","url":null,"abstract":"<p><p>It has been claimed that microRNA 503-5p (miR-503-5p) is the key to the future diagnosis and treatment of cardiac hemangioma (CH), but the relationship between the two has not been fully validated. In this study, we analyzed the effect of miR-503-5p targeting type IA bone morphogenetic protein receptor (BMPR1A) on CH to inform future diagnosis and treatment of CH. First, miR-503-5p and BMPR1A abnormal expression sequences (vectors) were transfected into human hemangioma-derived endothelial cells (HemECs) and human umbilical vein endothelial cells (HUVECs) to observe alterations in cell biological behavior, adhesion, and epithelial mesenchymal transition (EMT). We found enhanced proliferative, invasive and migrating abilities of HemECs and HUVECs after silencing miR-503-5p or increasing BMPR1A, accompanied by reduced apoptosis, elevated intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and accelerated EMT; after increasing miR-503-5p or silencing BMPR1A, the cells exhibited reduced apoptosis, elevated ICAM-1 and VCAM-1, and accelerated EMT (P<0.05). Subsequently, a dual-luciferase reporter assay was performed to analyze the targeting relationship between miR-503-5p and BMPR1A. The results showed that miR-503-5p inhibited BMPR1A-wild type (WT) fluorescence activity (P<0.05). Through the rescue experiment, it was observed that the biological behavior of the cells with simultaneous elevation or simultaneous silencing of miR-503-5p and BMPR1A was not different from that of cells transfected with BMPR1A empty vector (P>0.05), indicating that the effect of BMPR1A on cells was reversed by miR-503-5p. Finally, in the analysis of clinical records, we found that CH cases exhibited lower miR-503-5p and higher BMPR1A levels than healthy controls (P<0.05). The expression of the two genes was negatively correlated (P<0.05). These results suggest that miR-503-5p participates in CH growth by targeted sponging of BMPR1A.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5304-5320"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}