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- Title
Down-regulation of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer.
- Authors
Liu, Aihua; Zuo, Zhongfu; Liu, Linlin; Liu, Lihua
- Abstract
Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K–AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.
- Subjects
CELL growth; COLORECTAL cancer; MITOGEN-activated protein kinases; WESTERN immunoblotting; CELL migration
- Publication
Biochemistry & Cell Biology, 2020, Vol 98, Issue 5, p548
- ISSN
0829-8211
- Publication type
Article
- DOI
10.1139/bcb-2019-0351