RasGRP3 controls cell proliferation and migration in papillary thyroid cancer by regulating the Akt-MDM2 pathway
| Autor: | Minggao Guo, Xiaotian Xia, Zhongling Qiu, Zhili Yang, Wangwang Qiu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system diseases Down-Regulation Papillary thyroid cancer 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation Cell Movement Cell Line Tumor Genetics medicine Animals Guanine Nucleotide Exchange Factors Humans Thyroid Neoplasms RNA Small Interfering Protein kinase B Cell Proliferation Mice Inbred BALB C biology Cell growth Carcinoma Cancer Proto-Oncogene Proteins c-mdm2 General Medicine medicine.disease Carcinoma Papillary Up-Regulation Oncogene Protein v-akt 030104 developmental biology Cell culture Thyroid Cancer Papillary 030220 oncology & carcinogenesis biology.protein Cancer research Mdm2 ras Guanine Nucleotide Exchange Factors Guanine nucleotide exchange factor |
| Zdroj: | Gene. 633 |
| ISSN: | 1879-0038 |
| Popis: | Accumulating evidence has shown that Ras guanylnucleotide releasing peptide 3 (RasGRP3) is up-regulated in several distinct cancer types; however, its role in papillary thyroid cancer (PTC) remains unclear. In this study, we demonstrate that RasGRP3 was overexpressed in PTC tissues and cell lines. Downregulation of RasGRP3 using small interfering (si) RNA significantly inhibited PTC cell proliferation and migration in vitro, and tumor growth in vivo, reflecting an oncogenic role of RasGRP3 in PTC. We subsequently identified that the expression of mouse double minute 2 homolog (MDM2) and phosphorylated Akt (p-Akt) was significantly decreased in RasGRP3-downregulated PTC cells. Overexpression of MDM2 attenuated the function of si-RasGRP3. Taken together, our data show that RasGRP3 exerts its oncogenic effect in PTC through Akt-mediated MDM2 activation. RasGRP3 may serve as a potential new therapeutic target for PTC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect