REC8 promotes tumor migration, invasion and angiogenesis by targeting the PKA pathway in hepatocellular carcinoma
| Autor: | Qian Ding, Xiaoyu Jiang, Jie Yin, Jia Wang, Ai-Di Li, Jing Han, Huiqing Jiang, Zi-Jin Cui, Yun Bai, Xiao-Li Xie |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Cytoplasm Carcinoma Hepatocellular Angiogenesis Cell Cycle Proteins General Biochemistry Genetics and Molecular Biology Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans Neoplasm Invasiveness Neoplasm Metastasis Cell Proliferation Cell Nucleus Tube formation Chemistry Matrigel Invasion Assay Liver Neoplasms Hep G2 Cells General Medicine medicine.disease Cyclic AMP-Dependent Protein Kinases digestive system diseases Up-Regulation Gene Expression Regulation Neoplastic Blot 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research Immunohistochemistry Female alpha-Fetoproteins Signal Transduction |
| Zdroj: | Clinical and Experimental Medicine. 21:479-492 |
| ISSN: | 1591-9528 1591-8890 |
| DOI: | 10.1007/s10238-021-00698-9 |
| Popis: | REC8 is a member of the cohesin family, and its abnormal activation has been detected in cancer cells. This study explored the role and possible mechanism of REC8 in hepatocellular carcinoma (HCC). A total of 40 pairs of HCC and adjacent tissues were collected, and the clinical significance of REC8 expression in HCC was evaluated. REC8 expression in human HCC tissues and HCC cell lines was investigated by quantitative real-time PCR, Western blotting, immunohistochemistry and immunofluorescence staining. The biological functions of REC8 in HCC cell lines were detected by wound-healing assay, Matrigel invasion assay and tube formation assay. The proteins interacting with REC8 were identified by mass spectrometry after immunoprecipitation screening. There was a correlation between the high expression of REC8 and positive alpha-fetoprotein levels. The expression level of REC8 protein in HCC tissues was higher than that in adjacent tissues. REC8 has mainly located in the nucleus of HCC tissue cells and HCC cell lines, but it was expressed in the cytoplasm of adjacent normal tissue cells and hepatocytes. The results of wound healing, transwell invasion and tubular formation assays indicated that the overexpression of REC8 accelerated the metastasis of HCC in vitro; however, metastasis was suppressed after REC8 was silenced by small interference RNA. A total of 57 differentially expressed proteins were identified by mass spectrometry, and it was found that REC8 and PKA RII-α staining was colocalized in the nucleus. The expression levels of MMP-9 and VEGF-C were decreased after treatment with the PKA inhibitor H89. Overall, REC8 promotes the migration, invasion and angiogenesis of HCC cells through the PKA pathway. |
| Databáze: | OpenAIRE |
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