AUTHOR=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 

TITLE=Inhibition of NEK7 Suppressed Hepatocellular Carcinoma Progression by Mediating Cancer Cell Pyroptosis

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.812655

DOI=10.3389/fonc.2022.812655

ISSN=2234-943X

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 involves 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 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 xenograft mouse model was also suppressed following knockdown of NEK7 expression. Mechanistic studies revealed that knockdown of NEK7 in HCC cells significantly upregulated expression of pyroptosis markers such as NLRP3, Caspase-1 and GSDMD. Co-culture of HCC cells stimulated hepatic stellate cells activation by increasing p-ERK1/2 and α-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 a potential target for a new therapeutic strategy of HCC treatment.