Oncology Research最新文献

{"title":"Retraction: Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial-Mesenchymal Transition Process by Upregulation of MicroRNA-1284.","authors":"","doi":"10.32604/or.2024.055033","DOIUrl":"https://doi.org/10.32604/or.2024.055033","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504018X15172738893959.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 8","pages":"1377"},"PeriodicalIF":2.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763986","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":"Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.","authors":"Lisanne K A Neijenhuis, Leuta L Naumann, Sonia A M Ferkel, Samuel J S Rubin, Stephan Rogalla","doi":"10.32604/or.2024.050907","DOIUrl":"10.32604/or.2024.050907","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.</p><p><strong>Methods: </strong>In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration.</p><p><strong>Results: </strong>After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (<i>p</i> = 0.003) and 2% (<i>p</i> = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable.</p><p><strong>Conclusions: </strong>In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1163-1172"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469880","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":"Inflammatory myofibroblastic tumor from molecular diagnostics to current treatment.","authors":"Paulina Chmiel, Aleksandra SłOWIKOWSKA, Łukasz Banaszek, Anna Szumera-CIEćKIEWICZ, BARTłOMIEJ Szostakowski, Mateusz J SPAłEK, Tomasz Świtaj, Piotr Rutkowski, Anna M Czarnecka","doi":"10.32604/or.2024.050350","DOIUrl":"10.32604/or.2024.050350","url":null,"abstract":"<p><p>Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate. Diagnostic challenges arise from the diverse pathological presentation, variable symptomatology, and lack of different imaging features. However, IMT is identified by the fusion of the anaplastic lymphoma kinase (ALK) gene, which is present in approximately 70% of cases, with various fusion partners, including ran-binding protein 2 (RANBP2), which allows confirmation of the diagnosis. While surgery is the preferred approach for localized tumors, the optimal long-term treatment for advanced or metastatic disease is difficult to define. Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT. Crizotinib, an ALK tyrosine kinase inhibitor (TKI), was officially approved by the US Food and Drug Administration (FDA) in 2020 to treat IMT with ALK rearrangement. However, most patients face resistance and disease progression, requiring consideration of sequential treatments. Combining radiotherapy with targeted therapy appears to be beneficial in this indication. Early promising results have also been achieved with immunotherapy, indicating potential for combined therapy approaches. However, defined recommendations are still lacking. This review analyzes the available research on IMT, including genetic disorders and their impact on the course of the disease, data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication, as well as summarizing general knowledge about prognostic and predictive factors, also in terms of resistance to systemic therapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1141-1162"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469838","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":"IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.","authors":"Zhaoying Zhu, Yanjia Hu, Feng Ye, Haibo Teng, Guoliang You, Yunhui Zeng, Meng Tian, Jianguo Xu, Jin Li, Zhiyong Liu, Hao Liu, Niandong Zheng","doi":"10.32604/or.2024.042456","DOIUrl":"10.32604/or.2024.042456","url":null,"abstract":"<p><strong>Background: </strong>Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear.</p><p><strong>Methods: </strong>We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.</p><p><strong>Results: </strong>Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.</p><p><strong>Conclusions: </strong>IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1173-1184"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469837","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":"ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling.","authors":"Xia DA, Han Ge, Junfeng Shi, Chunhua Zhu, Guozhu Wang, Yuan Fang, Jin Xu","doi":"10.32604/or.2024.045433","DOIUrl":"10.32604/or.2024.045433","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC).</p><p><strong>Methods: </strong>ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR. ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis. The migration, invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.</p><p><strong>Results: </strong>ROR2 expression was high in metastatic TNBC tissues. ROR2 knockdown suppressed the migration, invasion and chemoresistance of TNBC cells. ROR2 overexpression in MDA-MB-435 cells promoted the migration, invasion, and chemoresistance. Moreover, ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin. ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.</p><p><strong>Conclusion: </strong>ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1209-1219"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469840","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":"Trametinib boosts palbociclib's efficacy in breast cancer via autophagy inhibition.","authors":"Anguo Wu, Jiao Yan, Ting Su, Chi Feng, Xin Long, Yiru Pan, Rupei Ye, Tian Xia, Hanan Long, Jianming Wu, Xiuli Xiao","doi":"10.32604/or.2024.046139","DOIUrl":"10.32604/or.2024.046139","url":null,"abstract":"<p><p>Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both <i>in vitro</i> (MCF7 and MDA-MB-468 cells) and <i>in vivo</i> (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and <i>in vivo</i> studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1197-1207"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469843","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":"LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis.","authors":"Yuanlin Liu, Yan Liu, Yan Wang, Qiang Wang, Yan Yan, Dandan Zhang, Huiqin Liu","doi":"10.32604/or.2024.047454","DOIUrl":"10.32604/or.2024.047454","url":null,"abstract":"<p><p>At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p down-regulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1221-1229"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469839","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":"Silencing of the long non-coding RNA <i>LINC00265</i> triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene.","authors":"Xiaobi Huang, Chunyuan Chen, Yongyang Chen, Honglian Zhou, Yonghua Chen, Zhong Huang, Yuliu Xie, Baiyang Liu, Yudong Guo, Zhixiong Yang, Guanghua Chen, Wenmei Su","doi":"10.32604/or.2023.030771","DOIUrl":"10.32604/or.2023.030771","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. <i>LINC00265</i> is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood.</p><p><strong>Methods: </strong>Here, the regulatory role of <i>LINC00265</i> in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts.</p><p><strong>Results: </strong>We found that high levels of <i>LINC00265</i> expression were associated with shorter overall survival rate of patients, whereas knockdown of <i>LINC00265</i> inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of <i>LINC00265</i> induced autophagy and apoptosis. Moreover, we showed that <i>LINC00265</i> interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that <i>LINC00265</i> functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma.</p><p><strong>Conclusions: </strong>Our findings thus identify SIN3A as a <i>LINC00265</i>-associated protein and should help to understand the mechanism underlying <i>LINC00265</i>-mediated oncogenesis.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1185-1195"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469841","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":"The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines.","authors":"Mohammad-Taghi Moradi, Dhiya Altememy, Majid Asadi-Samani, Pegah Khosravian, Marziyeh Soltani, Leila Hashemi, Azadeh Samiei-Sefat","doi":"10.32604/or.2024.047187","DOIUrl":"10.32604/or.2024.047187","url":null,"abstract":"<p><strong>Background: </strong>Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257).</p><p><strong>Materials and methods: </strong>In this <i>in vitro</i> study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry.</p><p><strong>Results: </strong>Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (<i>p</i> < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.</p><p><strong>Conclusions: </strong>Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 7","pages":"1231-1237"},"PeriodicalIF":2.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469842","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":"<i>GNAS</i> mutations suppress cell invasion by activating MEG3 in growth hormone-secreting pituitary adenoma.","authors":"Chao Tang, Chunyu Zhong, Junhao Zhu, Feng Yuan, Jin Yang, Yong Xu, Chiyuan Ma","doi":"10.32604/or.2024.046007","DOIUrl":"10.32604/or.2024.046007","url":null,"abstract":"<p><p>Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in <i>GNAS</i> (α subunit of stimulatory G protein). Mutations in <i>GNAS</i> are associated with clinical features of smaller and less invasive tumors. However, the role of <i>GNAS</i> mutations in the invasiveness of GHPAs is unclear. <i>GNAS</i> mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (<i>MEG3</i>) was evaluated with RT-qPCR. <i>MEG3</i> was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of <i>MEG3</i> on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated <i>GNAS</i> compared with that in mice with wild-type <i>GNAS</i>. Consistently, the invasiveness of mutant <i>GNAS</i>-expressing GH3 cells decreased. <i>MEG3</i> is uniquely expressed at high levels in GHPAs harboring mutated <i>GNAS</i>. Accordingly, <i>MEG3</i> upregulation inhibited tumor cell invasion, and conversely, <i>MEG3</i> downregulation increased tumor cell invasion. Mechanistically, <i>GNAS</i> mutations inhibit EMT in GHPAs. <i>MEG3</i> in mutated <i>GNAS</i> cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated <i>in vivo</i>. Our data suggest that <i>GNAS</i> mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the <i>MEG3/Wnt/β-catenin</i> signaling pathway.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 6","pages":"1079-1091"},"PeriodicalIF":2.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11136687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198988","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}