miR-17~92 Suppresses Proliferation and Invasion of Cervical Cancer Cells by Inhibiting Cell Cycle Regulator Cdt2

Cervical cancer (CC) is 4th largest killer of women worldwide when diagnosed in late stages the treatment options are almost negligible. 99% of CC is caused by high risk human papilloma viruses (HR-HPV). Upon integration into human genome the encoded viral proteins mis-regulates various onco-suppressor and checkpoint factors including cell cycle regulators. One such factor is cell cycle S phase licensing factor Cdt2, which has been reported to be highly upregulated in various cancers including CC. HPV proteins also suppress several tumor suppressor miRNAs concluding miR-17-92 cluster. In this study we report that miR-17-92 directly recruits to 3UTR of Cdt2 and downregulates this oncogene which suppresses the proliferation, migration, invasion capabilities of the CC cell lines while normal cells are fine. Suppression of Cdt2 by miR17-92 blocks the cancerous cells in S phase and induces apoptosis eventually leading to their death. Hence, our work for the first time mechanistically shows how miR17-92 could work as tumor suppressor opening up the potential of miR17-92 to be used in developing therapy for cervical cancer treatment.