HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer death in women. Human papillomavirus (HPV16) E6/E7 heterogenous expression in C33A cells increased the mRNA and protein levels of KIF2A, while siRNA deletion of endogenous E6/E7 reduced the mRNA and protein levels of KIF2A in SiHa cells. KIF2A promoted cell migration and invasion, and regulated the expression of epithelial-mesenchymal transition-related proteins in C33A and SiHa cells. The exogenous expression of E6/E7 in C33A cells increased the phosphorylation of Akt, ERK, and JNK. However, Akt (API-2) and ERK (PD98059) inhibitors had no effect on the increase in KIF2A expression induced by E6/E7, while JNK inhibitors (JNK-IN-8 and SP600125) blocked the increase in KIF2A expression induced by E6/E7. The exogenous expression of E6/E7 increased the levels of transcription factor c-Jun, which is the classic substrate of JNK. Knockdown of c-Jun reduced the increase in KIF2A expression induced by E6/E7. In summary, KIF2A plays a key role in the motility and metastasis of cervical cancer. HPV16 E6/E7 can increase the levels of transcription factor c-Jun by activating the JNK signal, thereby up-regulating the transcriptional expression of KIF2A.

Automated summary

KIF2A plays a key role in the motility and metastasis of cervical cancer, and HPV16 E6/E7 up-regulates the transcriptional expression of KIF2A by activating JNK signaling pathway.