NEK7 overexpression contributes to stemness of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the cancers with the highest mortality rates worldwide, being the sixth most commonly diagnosed cancer globally and the third leading cause of cancer-related deaths. Growing evidence suggests that tumor initiation can be driven by a cancer stem cell (CSC) subset, which is responsible for tumor persistence, relapse, metastasis, chemo-resistance, and radio-resistance, establishing CSCs as important therapeutic targets. Identification and characterization of functional pathways and biomarkers associated with CSC biology will provide useful information for developing novel treatment strategies against HCC. NIMA Related Kinase 7 (NEK7) is a serine/threonine kinase that plays an important role in regulating gene transcription or protein expression of the NLRP3 inflammasome signaling pathway. We have observed that the expression level of NEK7 is significantly elevated in HCC tissues compared to surrounding normal tissues, therefore, we initially investigated whether NEK7 targeting could suppress HCC proliferation. As expected, siRNA silencing of NEK7 effectively inhibited the growth of HCC cell lines such as Huh7, HepG2, and PLC/PRF/5. Based on the previous report that the treatment of vitamin D suppressed stemness of CD133 + /CD44 + CSCs by reducing NLRP3 expression in triple-negative breast cancer, we next determined to observe if targeting of NEK7 could suppress the metastatic potential of HCC as well. Inhibition of NEK7 expression reduced the abilities of migration, invasion, and sphere formation of both parental HCC cell populations (of Huh7, HepG2, and PLC/PRF/5) and CD133 + liver CSCs (isolated from PLC/PRF/5). Our findings suggest that NEK7 contributes HCC stemness, indicating its potential as a therapeutic target for treating primary HCC and preventing metastasis and/or recurrence.