IL-6/STAT3 Mediates the HPV18 E6/E7 Stimulated Upregulation of MALAT1 Gene in Cervical Cancer HeLa Cells

MALAT1, a long non-coding RNA, is highly expressed in cervical cancer cells and plays an important role in the development of cervical cancer. However, the mechanism for the excessive expression of MALAT1 in cervical cancer remains unclear. High-risk HPVs are causative agents of cervical cancer and the IL-6/STAT3 signaling is closely correlated with the development of various cancers including cervical cancer. In this study, the roles of HPV18 E6/E7 and IL-6/STAT3 in the regulation of MALAT1 transcription in cervical cancer cells were investigated. It was found that HPV18 E6/E7 activated the IL-6/STAT3 signaling and, in reciprocal, IL-6/STAT3 strengthened HPV18 E6/E7 expression in HeLa cells. Both HPV18 E6/E7 and IL-6/STAT3 were involved in MALAT1 expression and they worked synergistically in the upregulation of MALAT1 gene. With luciferase reporter assays, a STAT3-binding sequence in the enhancer region of MALAT1 gene was demonstrated to be crucial for the IL-6- or STAT3-induced MALAT1 promoter activation. Taken together, our data suggest that IL-6/STAT3 mediates the HPV18 E6/E7 stimulated upregulation of MALAT1 gene in cervical cancer HeLa cells.