E6 hijacks KDM5C/lnc_000231/miR‐497‐5p/CCNE1 axis to promote cervical cancer progression

Emerging evidence suggests that long non‐coding RNA (lncRNA) plays an important role in disease development, particularly in cancers. Recent studies with genome‐wide sequencing on cervical squamous cell carcinoma and matched adjacent non‐tumour tissues showed that a newly identified lncRNA‐lnc_000231 was highly expressed in cervical cancers. However, the underlying mechanism through which it is activated and its role in cervical cancer progression is still unclear. In this study, first, we confirmed that lnc_000231 is up‐regulated in cervical cancer cells and tumour tissues. Mechanically, we demonstrated that E6 up‐regulates lnc_000231 expression through promoting its promoter region H3K4me3 modification by destabilizing KDM5C. In vitro and in vivo results showed that lnc_000231 promotes cervical cancer cell proliferation and tumour formation by acting as miR‐497‐5p sponge and maintaining cyclin E1 (CCNE1) expression. Thus, our studies identified a new signalling pathway through which E6 promotes cervical cancer progression. E6 hijacked KDM5C/lnc_000231/miR‐497‐5p/CCNE1 signalling pathway is a promising target for cervical cancer treatment in the future.