scholarly journals U1 snRNP regulates cancer cell migration and invasion

2019 ◽  
Author(s):  
Jung-Min Oh ◽  
Christopher C. Venters ◽  
Chao Di ◽  
Anna Maria Pinto ◽  
Lili Wan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Migration And Invasion ◽  
Small Nuclear Rna ◽  
Mrna Isoforms ◽  
Over Expression ◽  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Antisense Morpholino ◽  
Polyadenylation Signals

AbstractStimulated cells and cancer cells have widespread shortening of mRNA 3’-utranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in the last exon and in introns. U1 snRNA (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread mRNA shortening. Here we show that U1 AMO also modulates cancer cells’ phenotype, dose-dependently increasing migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected link between U1 regulation and oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

scholarly journals U1 snRNP regulates cancer cell migration and invasion in vitro

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jung-Min Oh ◽  
Christopher C. Venters ◽  
Chao Di ◽  
Anna Maria Pinto ◽  
Lili Wan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Migration And Invasion ◽  
Small Nuclear Rna ◽  
Mrna Isoforms ◽  
Over Expression ◽  
U1 Snrnp ◽  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Antisense Morpholino

AbstractStimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

IL-24 inhibits the malignancy of human glioblastoma cells via destabilization of Zeb1

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tie Lin ◽  
Dongpeng Wang ◽  
Jun Chen ◽  
Zhan Zhang ◽  
Yuming Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cancer Cells ◽  
Mrna Stability ◽  
Epithelial To Mesenchymal Transition ◽  
Migration And Invasion ◽  
Malignant Tumours ◽  
Mesenchymal Transition ◽  
Over Expression ◽  
The Central Nervous System

Abstract Glioblastoma (GBM) is the most common and fatal type of primary malignant tumours in the central nervous system. Cytokines such as interleukins (ILs) play an important role in GBM progression. Our present study found that IL-24 is down-regulated in GBM cells. Recombinant IL-24 (rIL-24) can suppress the in vitro migration and invasion of GBM cells while increase its chemo-sensitivity to temozolomide (TMZ) treatment. rIL-24 negatively regulates the expression of Zeb1, one well known transcription factors of epithelial to mesenchymal transition (EMT) of cancer cells. Over expression of Zeb1 can attenuate IL-24-suppressed malignancy of GBM cells. Mechanistically, IL-24 decreases the protein stability of Zeb1 while has no effect on its mRNA stability. It is due to that IL-24 can increase the expression of FBXO45, which can destabilize Zeb1 in cancer cells. Collectively, we reveal that IL-24 can suppress the malignancy of GBM cells via decreasing the expression of Zeb1. It suggests that targeted activation of IL-24 signals might be a potential therapy approach for GBM treatment.

scholarly journals CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Dawei Rong ◽  
Chen Lu ◽  
Betty Zhang ◽  
Kai Fu ◽  
Shuli Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Gastric Cancer Cells ◽  
Over Expression ◽  
Tensin Homolog

Abstract Background Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure, but its functions remain largely unknown. Growing evidence has revealed that circRNAs play a striking role as functional RNAs in the progression of malignant disease. However, the precise role of circRNAs in gastric cancer (GC) remains unclear. Methods CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase reaction. Luciferase reporter, RNA pull down, and fluorescence in situ hybridization assays were employed to test the interaction between circPSMC3 and miR-296-5p. Ectopic over-expression and siRNA-mediated knockdown of circPSMC3, proliferation, migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPSMC3. Results CircPSMC3 rather than liner PSMC3 mRNA was down-regulated in GC tissues, corresponding plasmas from GC patients as well as GC cell lines compared to normal controls. Lower circPSMC3 expression in GC patients was correlated with higher TNM stage and shorter overall survival. Over-expression of circPSMC3 and miR-296-5p inhibitor could inhibit the tumorigenesis of gastric cancer cells in vivo and vitro whereas co-transfection of circPSMC3 and miRNA-296-5p could counteract this effect. Importantly, we demonstrated that circPSMC3 could act as a sponge of miR-296-5p to regulate the expression of Phosphatase and Tensin Homolog (PTEN), and further suppress the tumorigenesis of gastric cancer cells. Conclusion Our study reveals that circPSMC3 can serve as a novel potential circulating biomarker for detection of GC. CircPSMC3 participates in progression of gastric cancer by sponging miRNA-296-5p with PTEN, providing a new insight into the treatment of gastric cancer.

In vitro Correction of a Novel Splicing Alteration in the BTK Gene by Using Antisense Morpholino Oligonucleotides

2014 ◽  
Vol 62 (5) ◽  
pp. 431-436 ◽  
Author(s):  
Natthakorn Rattanachartnarong ◽  
Siraprapa Tongkobpetch ◽  
Pantipa Chatchatee ◽  
Tassalapa Daengsuwan ◽  
Chupong Ittiwut ◽  
...  
Keyword(s):  
Morpholino Oligonucleotides ◽  
Antisense Morpholino Oligonucleotides ◽  
Antisense Morpholino

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

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