Dataset Information

Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway.

ABSTRACT: SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ERK1/2 (pERK1/2), whereas the knockdown of SUN5 yielded the opposite results. PD0325901 decreased the level of pERK1/2 to inhibit cell proliferation and migration, which was partially reversed by SUN5 overexpression, indicating that drug resistance existed in patients with high SUN5 expression. The xenograft transplantation experiment showed that SUN5 accelerated tumor formation in vivo. Furthermore, we found that SUN5 regulated the ERK pathway via Nesprin2 mediation and promoted the nuclear translocation of pERK1/2 by interacting with Nup93. Thus, these findings indicated that highly expressed SUN5 promoted CRC proliferation and migration by regulating the ERK pathway, which may contribute to the clinical diagnosis and new treatment strategies for CRC.

SUBMITTER: Song X

PROVIDER: S-EPMC9654567 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway.

Song Xiaoyue X Li Ruhong R Liu Gang G Huang Lihua L Li Peng P Feng Wanjiang W Gao Qiujie Q Xing Xiaowei X

Cancers 20221031 21

SUN5 was first identified as a nuclear envelope protein involved in spermatocyte division. We found that SUN5 was highly expressed in some cancers, but its function and mechanism in cancer development remain unclear. In the present study, we demonstrated that SUN5 was highly expressed in colorectal cancer (CRC) tissues and cells, as indicated by bioinformatics analysis, and SUN5 promoted cell proliferation and migration in vitro. Moreover, the overexpression of SUN5 upregulated phosphorylated ER ...[more]

PMID: 36358787

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Project description:BackgroundThis paper aims to explore the effects of plasminogen activator, urokinase (PLAU) expression on the migration, invasion, and proliferation of colorectal cancer (CRC) cells and to preliminarily analyze its possible mechanism, thereby laying a foundation for the research on potential biological targets of CRC.MethodsCRC-related mRNA was screened in Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/gds/). Differentially expressed genes (DEGs) were obtained for functional enrichment analysis. The enriched pathway and key involved functional gene were screened for further in vitro and in vivo analysis CRC cells were transfected with PLAU-NC (negative control), PLAU-mimic, and PLAU-inhibitor for 48 h and divided into the above groups for later studies. The migration, invasion, and proliferation capacities of CRC cells were detected using wound healing, Transwell, and colony formation assays, respectively. The Src inhibitor saracatinib (AZD0530) was added to the PLAU-NC and PLAU-mimic groups, and the expression levels of Src/extracellular signal-regulated kinase (ERK) pathway-, migration-, invasion-, and proliferation-related proteins were detected by Western blotting.ResultsThe results showed that after upregulation of PLAU, the number of CRC cells (SW480) that migrated to the center of the wound significantly increased, the number of cells that migrated and invaded through the basement membrane increased in the PLAU-mimic group, and the number of colonies also increased. These results suggest that increasing PLAU expression promotes the migration, invasion, and proliferation of CRC cells. At the same time, the molecular mechanism of PLAU in CRC cells was investigated by downregulating the protein expression of Src combined with the results of the bioinformatics analysis. Western blotting revealed that the protein expressions of phosphorylated Src (p-Src) and phosphorylated ERK (p-ERK) in SW480 and SW620 cells increased significantly in the PLAU-mimic group compared with the PLAU-NC group, while the results were the opposite in the PLAU-inhibitor group. After being treated with saracatinib, we observed significantly decreased protein levels of p-ERK, matrix metallopeptidase 2 (MMP-2), MMP-3, MMP-9, Cyclin D1, and Cyclin A2 in the SW480 cells.ConclusionsIn conclusion, PLAU affects the migration, invasion, and proliferation of CRC cells by activating the Src/ERK pathway.

Dataset Information

Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway.

Publications

Nuclear Membrane Protein SUN5 Is Highly Expressed and Promotes Proliferation and Migration in Colorectal Cancer by Regulating the ERK Pathway.

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