scholarly journals AKT1 Inhibitory DNAzymes Inhibit Cell Proliferation and Migration of Thyroid Cancer Cells

2013 ◽  
Vol 14 (4) ◽  
pp. 2571-2575 ◽  
Author(s):  
Le Yang ◽  
Jin-Ting He ◽  
Hong Guan ◽  
Ya-Dong Sun
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Thyroid Cancer Cells ◽  
Inhibit Cell Proliferation ◽  
Proliferation And Migration

scholarly journals AXL/GAS6 Inhibition Induces Apoptosis and Suppresses Cell Proliferation and Migration by Blocking the PI3K/AKT Signaling Pathways in Thyroid Cancer Cells in Vivo

2022 ◽  
Author(s):  
Zhenhua Zhang ◽  
Zijie Su ◽  
Ji Zhang
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Akt Pathway ◽  
Protein Expressions ◽  
And Migration ◽  
Thyroid Cancer Cells ◽  
Proliferation And Migration

Abstract Background: The Gas6/Axl-PI3K/Akt pathway is known as one of the most critical molecular signaling pathways involved in the regulation of key cellular processes. GAS6 has emerged as the perfect target for many malignancy treatments, but its role in thyroid cancer remains less described. This study aimed to evaluate both knockdown and overexpression effects of GAS6 on thyroid cancer cell proliferation, migration, and viability.Methods: Both RT-PCR and western blot analysis were performed to evaluate mRNA and protein expressions of GAS6; cell viability was assessed by MTT assay; then, TUNEL apoptosis, Transwell and migration assays were monitored to determine the effects of GAS6 knockdown or GAS6 overexpression on 850-5C and CAL62 thyroid cancer cells. Results: The mRNAs and protein expressions of GAS6 were the highest in CAL62 cancer cells. AXL/GAS6 knockdown through the application of siGAS6 and XL184, an AXL inhibitor, strongly diminished the proliferation and migration levels of CAL62 by inducing cell apoptosis. Meanwhile, overexpression of GAS6 produced the inversed effects, and the protein levels of PI3K, AKT, and p-AKT were significantly up and downregulated, accordingly. Conclusion: GAS6 inhibition promotes apoptosis and represses the proliferation of thyroid cancer cells by activating PI3K/AKT pathway; thus, provides a novel target for thyroid cancer therapy.

scholarly journals A 5′-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Litao Han ◽  
Hejing Lai ◽  
Yichen Yang ◽  
Jiaqian Hu ◽  
Zhe Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Alternative Splicing ◽  
Papillary Thyroid Cancer ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Papillary Thyroid ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. Methods Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. Results Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. Conclusions Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Inhibit Endometrial Cancer Cell Proliferation and Migration through Delivery of Exogenous miR-302a

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xin Li ◽  
Li li Liu ◽  
Ju lei Yao ◽  
Kai Wang ◽  
Hao Ai
Keyword(s):  
Cell Proliferation ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Target Cells ◽  
Human Umbilical Cord ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

MicroRNAs (miRNAs) are potential therapeutic targets in endometrial cancer, but the difficulties associated with their delivery to tumor target cells have hampered their applications. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a well-recognized tumor-homing ability, emphasizing the capacity of tumor-targeted delivery of extracellular vesicles. hUCMSCs release extracellular vesicles rich in miRNAs, which play a vital role in intercellular communication. The purpose of this study was to verify a potential tumor suppressor microRNA, miR-302a, and engineered hUCMSC extracellular vesicles enriched with miR-302a for therapy of endometrial cancer. Here, we observed that miR-302a was significantly downregulated in endometrial cancer tissues when compared with adjacent tissues. Overexpression of miR-302a in endometrial cancer cells robustly suppressed cell proliferation and migration. Meanwhile, the proliferation and migration were significantly inhibited in endometrial cancer cells when cultured with miR-302a-loaded extracellular vesicles derived from hUCMSCs. Importantly, our data showed that engineered extracellular vesicles rich in miR-302 significantly inhibited the expression of cyclin D1 and suppressed AKT signaling pathway in endometrial cancer cells. These results suggested that exogenous miR-302a delivered by hUCMSC-derived extracellular vesicles has exciting potential as an effective anticancer therapy.

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