Abstract
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.
Highlights
Cervical cancer is one of the most common malignancies in women worldwide, with estimated 529,000 new cases and 275,000 deaths each year
We found that the expression of miR-2861 was reduced in those with the advanced tumor stage or lymph node metastasis (Fig. 3F,G), indicating that miR-2861 may act as a tumor suppressor in cervical cancer
We subsequently examined whether EGFR, AKT2, and CCND1 could counteract the effect of miR-2861
Summary
Cervical cancer is one of the most common malignancies in women worldwide, with estimated 529,000 new cases and 275,000 deaths each year (www.who.int/hpvcentre). Persistent infection by oncogenic human papillomaviruses (HPVs) is widely recognized as the leading cause of cervical cancer[1]. MiRNAs encoded by HPV have not been identified, several host miRNAs are involved in HPV induced cervical cancer initiation and progression, such as miR-42422, miR-37523, miR-34a24,25, miR-21826, miR-23b27, and miR-20328. It is conceivable that cellular miRNAs can participate directly in the carcinogenic procedure induced by HPV oncoproteins. As HPV16 is by far the most common cancer-related HPV type, in the current study, we sought to determine miRNA expression profiles in response to HPV16 oncoprotein E6 overexpression by microarray analysis to identify specific cellular miRNAs that play biological roles in HPV16 E6 induced cancer. We identified a new pathway employing miR-2861, EGFR, AKT2, and CCND1 that mediates HPV16 E6 induced initiation and progression of cervical cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
