Persistent infection with oncogenic human papillomavirus viruses (HPVs) is a casual factor for cervical cancer and its precursors， and the abnormal constitutive expression of viral oncoprotein E6 is a key event during the malignant transformation. Here， we performed miRNA microarray to identify changes of miRNAs following ectopic HPV16 E6 overexpression in HEK293T cells and found miR-2861 was greatly decreased in both HEK293T and HaCaT cells expressing HPV16 E6 compared to vector control. Further， we demonstrated a biological link among HPV16 E6， miR-2861， EGFR， AKT2， and CCND1 in cervical cancer cells. We showed that miR-2861 was downregulated in cervical cancer tissues and negatively correlated ... More
Persistent infection with oncogenic human papillomavirus viruses (HPVs) is a casual factor for cervical cancer and its precursors， and the abnormal constitutive expression of viral oncoprotein E6 is a key event during the malignant transformation. Here， we performed miRNA microarray to identify changes of miRNAs following ectopic HPV16 E6 overexpression in HEK293T cells and found miR-2861 was greatly decreased in both HEK293T and HaCaT cells expressing HPV16 E6 compared to vector control. Further， we demonstrated a biological link among HPV16 E6， miR-2861， EGFR， AKT2， and CCND1 in cervical cancer cells. We showed that miR-2861 was downregulated in cervical cancer tissues and negatively correlated with advanced tumor stage and lymph node metastasis. Overexpression of miR-2861 suppressed cervical cancer cell proliferation and invasion and enhanced apoptosis. Subsequent investigation revealed that EGFR， AKT2， and CCND1 were all the direct targets of miR-2861. Importantly， silencing EGFR， AKT2， and/or CCND1 recapitulated the cellular effects seen upon miR-2861 overexpression. Restoration of EGFR， AKT2， and/or CCND1 counteracted the effects of miR-2861 expression. Thus， we identified a new pathway employing miR-2861， EGFR， AKT2， and CCND1 that may mediate HPV16 E6 induced initiation and progression of cervical cancer.
