| Title | Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis |
| Authors | Yan, Zilong Da, Qingen Li, Zhangfu Lin, Qirui Yi, Jing Su, Yanze Yu, Guanyin Ren, Qingqi Liu, Xu Lin, Zewei Qu, Jianhua Yin, Weihua Liu, Jikui |
| Affiliation | Peking Univ, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Shenzhen Hosp, Dept Hepatobiliary Surg, Shenzhen, Peoples R China Peking Univ, Shenzhen Hosp, Dept Hepatobiliary Surg, Shenzhen, Peoples R China Peking Univ, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Dept Cardiovasc Surg, Shenzhen, Peoples R China Peking Univ, Shenzhen Hosp, Dept Pathol, Shenzhen, Peoples R China |
| Keywords | NLRP3 INFLAMMASOME THERAPY TARGET SURVIVAL ACTIVATION MECHANISMS EXPRESSION CASPASES KINASES DEATH |
| Issue Date | 10-Feb-2022 |
| Publisher | FRONTIERS IN ONCOLOGY |
| Abstract | NIMA-related kinase 7 (NEK7) is a serine/threonine kinase involved in cell cycle progression via mitotic spindle formation and cytokinesis. It has been related to multiple cancers, including breast cancer, hepatocellular cancer, lung cancer, and colorectal cancer. Moreover, NEK7 regulated the NLRP3 inflammasome to activate Caspase-1, resulting in cell pyroptosis. In the present study, we investigated whether NEK7 is involved in cell pyroptosis of hepatocellular carcinoma (HCC). Interestingly, we found that NEK7 was significantly related to expression of pyroptosis marker GSDMD in HCC. We found that NEK7 expression was significantly correlated with GSDMD expression in bioinformatics analysis, and NEK7 expression was significantly co-expressed with GSDMD in our HCC specimens. Cell viability, migration, and invasion capacity of HCC cell lines were inhibited, and the tumor growth in the xenograft mouse model was also suppressed following knockdown of NEK7 expression. Mechanistic studies revealed that knockdown of NEK7 in HCC cells significantly upregulated the expression of pyroptosis markers such as NLRP3, Caspase-1, and GSDMD. Coculture of HCC cells stimulated hepatic stellate cell activation by increasing p-ERK1/2 and alpha-SMA. Knockdown of NEK7 impaired the stimulation of HCC cells. Therefore, downregulation of NEK7 inhibited cancer-stromal interaction by triggering cancer cell pyroptosis. Taken together, this study highlights the functional role of NEK7-regulated pyroptosis in tumor progression and cancer-stromal interaction of HCC, suggesting NEK7 as a potential target for a new therapeutic strategy of HCC treatment. |
| URI | http://hdl.handle.net/20.500.11897/638555 |
| ISSN | 2234-943X |
| DOI | 10.3389/fonc.2022.812655 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳医院 |
