宫颈癌（CC）是全球妇女死亡的第四大原因，如果在晚期被诊断出来，治疗选择几乎没有。99%的CC由高风险人乳头瘤病毒（HR-HPV）引起。当HR-HPV整合到人类基因组中时，编码的病毒蛋白误调节多种抑癌因子和细胞周期调节因子，包括细胞周期S期获得许可因子CDC-10依赖的转录物-2（Cdt2）。已有报道表明，在多种癌症中，包括CC，Cdt2高度上调。同时，在CC细胞中，数种抑癌miRNA被抑制，其中包括miR-17 ~ 92簇。本研究报告了miR-17 ~ 92直接招募到Cdt2的3'UTR上，并下调这一癌基因，抑制了CC细胞系的增殖、迁移和侵袭能力，而不影响非癌细胞。我们进一步表明，miR-17 ~ 92通过抑制Cdt2，阻滞了癌细胞进入S期并诱导凋亡，最终导致它们的死亡。因此，我们的工作首次阐明了miR-17 ~ 92在宫颈癌细胞中作为抑癌基因的机制，为将miR-17 ~ 92用于宫颈癌治疗的开发开辟了潜力。© 2023. Springer Science+Business Media, LLC.

Cervical cancer (CC) is the 4th most leading cause of death among women worldwide, and if 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-regulate various onco-suppressors and checkpoint factors including cell cycle regulators. One such protein is cell cycle S phase licensing factor, CDC-10 dependent transcript-2 (Cdt2) which has been reported to be highly upregulated in various cancers including CC. Also, in CC cells, several tumor suppressor miRNAs are suppressed, including miR-17 ~ 92 cluster. In this study, we report that miR-17 ~ 92 directly recruits to 3'UTR of Cdt2 and downregulates this oncogene which suppresses the proliferation, migration and invasion capabilities of the CC cell lines without affecting non-cancerous cells. We further show that suppression of Cdt2 by miR-17 ~ 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 miR-17 ~ 92 could work as tumor suppressor in cervical cancer cells, opening up the potential of miR-17 ~ 92 to be used in developing therapy for cervical cancer treatment.© 2023. Springer Science+Business Media, LLC.