A novel long non-coding RNA XLOC_004787, is associated with migration and promotes cancer cell proliferation by downregulating mir-203a-3p in gastric cancer

BMC Gastroenterology, Год журнала: 2023, Номер 23(1)

Опубликована: Авг. 12, 2023

Abstract Background Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms cancer. However, the roles most lncRNAs progression gastric cancer (GC) remain largely unexplored. This study investigates biological function and underlying mechanism novel lncRNA, XLOC_004787 GC. Methods The location GES-1 cells HGC-27 were detected by fluorescence situ hybridization (FISH) assay. expression levels assessed using quantitative real-time PCR (qRT-PCR) cell lines, GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, cells. Functional assays such Transwell migration, counting kit-8 (CCK-8), colony formation experiments employed to analyze effects miR-203a-3p on migration proliferation. Protein associated with GC these lines examined Western blotting. intracellular localization β-catenin P-Smad2/3 was immunofluorescence (IF) Additionally, interaction between investigated dual luciferase Results localized at both cytoplasm nucleus Compared normal tissues cells, significantly upregulated highest lowest observed SGC-7901 respectively. Furthermore, reduced seen inhibit proliferation blotting analysis revealed that decrease correspondingly decreased N-cadherin, mmp2, mmp9, Snail, Vimentin, β-catenin, C-myc, Cyclin D1, TGF-β, while concurrently increasing E-cadherin expression. also diminished relation Smad2/3, P-Gsk3β comparison Gsk3β. nuclear entry lower Amplifying via pcDNA_XLOC_004787 suggested potential for promotion. Notably, found negatively regulate mir-203a-3p expression, binding sites two. Higher proliferation, enhance Conversely, suppression promotion Conclusions These results suggest XLOC_004787, be tissues, potentially promotes occurs through activation TGF-β Wnt/β-catenin signaling pathways EMT-related proteins. may influence modulating pathway adsorption inhibition mir-203a-3p.

Язык: Английский

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CD40 is expressed in the subsets of endothelial cells undergoing partial endothelial–mesenchymal transition in tumor microenvironment

Cancer Science, Год журнала: 2023, Номер 115(2), С. 490 - 506

Опубликована: Дек. 18, 2023

Abstract Tumor progression and metastasis are regulated by endothelial cells undergoing endothelial–mesenchymal transition (EndoMT), a cellular differentiation process in which lose their properties differentiate into mesenchymal cells. The EndoMT through spectrum of intermediate phases, suggesting that some remain partial state exhibit an endothelial/mesenchymal phenotype. However, detailed analysis has been hampered the lack specific markers. Transforming growth factor‐β (TGF‐β) plays central role induction EndoMT. Here, we showed inhibition TGF‐β signaling suppressed human oral cancer cell xenograft mouse model. By using genetic labeling lineage, also established novel reporter system, (EMRECs), allow visualization sequential changes during TGF‐β‐induced Using EMRECs, characterized gene profiles multiple stages identified CD40 as EndoMT‐specific marker. expression was upregulated EndoMT, but decreased full Furthermore, single‐cell RNA sequencing tumors revealed enriched population expressing both Moreover, EMRECs enhanced expressed inhibits to present findings provide better understanding mechanisms underlying will facilitate development therapeutic strategies targeting EndoMT‐driven metastasis.

Язык: Английский

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Functional analysis and validation of oncodrive gene AP3S1 in ovarian cancer through filtering of mutation data from whole-exome sequencing

European journal of medical research, Год журнала: 2024, Номер 29(1)

Опубликована: Апрель 12, 2024

Abstract Background High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of cancer accounts for a significant portion cancer-related deaths worldwide. Despite advancements in treatment, overall survival rate HGSOC patients remains low, thus highlighting urgent need deeper understanding molecular mechanisms driving tumorigenesis identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as powerful tool somatic mutations alterations across entire exome, providing valuable insights into genetic drivers pathways underlying development progression. Methods Via analysis whole-exome results tumor samples from 90 patients, we compared mutational landscape with that TCGA to identify similarities differences. The data were subjected bioinformatics explore driver genes their functional roles. Furthermore, conducted basic medical experiments validate obtained analysis. Results revealed profile HGSOC, including BRCA1, BRCA2 TP53 mutations. AP3S1 weighted gene. Further expression demonstrated associations patient immune response. knockdown cells its regulatory role cell migration invasion through TGF-β/SMAD pathway. Conclusion This comprehensive provides insight targets targeted interventions. was identified being key player immunity prognosis, new perspectives personalized treatment strategies. findings this study contribute pathogenesis provide foundation improved outcomes disease.

Язык: Английский

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Transforming growth factor-β signals promote progression of squamous cell carcinoma by inducing epithelial-mesenchymal transition and angiogenesis

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 714, С. 149965 - 149965

Опубликована: Апрель 17, 2024

At present, the molecular mechanisms driving progression and metastasis of oral squamous cell carcinoma (OSCC) remain largely uncharacterized. The activation transforming growth factor-β (TGF-β) signaling in tumor microenvironment has been observed various types cancer implicated their by enhancing migration invasion epithelial cells. However, its specific roles unexplored. In this study, we examined effects TGF-β on murine carcinoma, SCCVII cells vitro vivo. incubation with induced signals epithelial-mesenchymal transition (EMT). Notably, motility was increased upon signaling. RNA sequencing revealed upregulation genes related to EMT angiogenesis. Consistent these results, inhibition cell-derived primary tumors resulted suppressed Furthermore, identified six candidate factors (ANKRD1, CCBE1, FSTL3, uPA, TSP-1 integrin β3), whose expression cells, associated poor prognosis for patients head neck carcinoma. These results highlight role OSCC via multiple mechanisms, including angiogenesis, suggest novel therapeutic targets treatment OSCC.

Язык: Английский

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Special issue: TGF-β and epithelial-mesenchymal transition in cancer

Seminars in Cancer Biology, Год журнала: 2024, Номер 102-103, С. 1 - 3

Опубликована: Июнь 27, 2024

Язык: Английский

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