NUSAP1 knockdown inhibits cell growth and metastasis of non‐small‐cell lung cancer through regulating BTG2/PI3K/Akt signaling
| Autor: | Lan Wang, Fengxian Cui, Jian Xiong, Zheyuan Xu, Hao Peng, Yang Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Small interfering RNA Physiology Clinical Biochemistry Apoptosis Fumonisins Immediate-Early Proteins Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor Gene expression Humans Neoplasm Metastasis Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Gene knockdown BTG2 Chemistry Cell growth Tumor Suppressor Proteins Cell Biology respiratory tract diseases Gene Expression Regulation Neoplastic Oncogene Protein v-akt 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research Microtubule-Associated Proteins Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 235:3886-3893 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.29282 |
| Popis: | Non-small-cell lung cancer (NSCLC) is the most common malignancy along with high mortality rate worldwide. Recently, nucleolar and spindle-associated protein 1 (NUSAP1) has been reported to be involved in the malignant progression of several cancers. However, in NSCLC, the biological function of NUSAP1 and its molecular mechanism have not been reported. Here, our findings indicated that the NUSAP1 messenger RNA expression level was remarkably upregulated in NSCLC tissues compared with that of adjacent normal tissues. We also found that NUSAP1 gene expression was notably upregulated in NSCLC cell lines (A549, 95-D, H358, and H1299) compared with that of normal human bronchial epithelial cell line (16HBE). Subsequently, the biological function of NUSAP1 was investigated in A549 and H358 cells transfected with NUSAP1 small interfering RNA (siRNA), respectively. Results showed that NUSAP1 knockdown inhibited NSCLC cell proliferation, and promoted cell apoptosis. Furthermore, the number of cell migration and invasion was significantly suppressed by NUSAP1 knockdown. In addition, our results indicated that NUSAP1 knockdown increased the gene expression of B-cell translocation gene 2 (BTG2), but decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated serine/threonine kinase (p-AKT). BTG2 siRNA partly abrogates the effect of NUSAP1 knockdown on BTG2 gene expression. Fumonisin B1 (FB1), a AKT activator, reversed the effect of NUSAP1 knockdown on the biological function in NSCLC. Taken together, NUSAP1 knockdown promotes NSCLC cell apoptosis, and inhibits cell proliferation, cell migration, and invasion, which is associated with regulating BTG2/PI3K/Akt signal pathway. Our findings suggest that NUSAP1 is a promising molecular target for NSCLC treatment. |
| Databáze: | OpenAIRE |
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