Knockdown of MIR9‑3HG inhibits proliferation and promotes apoptosis of cervical cancer cells by miR‑498 via EP300

Abstract

Cervical cancer is a serious gynecological cancer and one of the primary causes of mortality in female patients with cancer. Despite advances in cancer research, the molecular mechanism underlying cancer remains poorly understood. High levels of MIR9-3 host gene (HG) are associated with the occurrence and development of cervical cancer. However, the specific role of MIR9-3HG during the development of cervical cancer is unclear. In the present study, the expression of MIR9-3HG was silenced in C33A and SiHa cervical cancer cell lines. Proliferation and apoptosis were measured in these cells using 5-ethynyl-2′-deoxyuridine assay and flow cytometry, respectively. In addition, targeting microRNAs (miRs) of MIR9-3HG and mRNAs of miR-498 were predicted using public databases. The predicted interactions between these molecules were validated using RNA immunoprecipitation, RNA pull-down and luciferase reporter assays. Lastly, C33A cells transfected with short hairpin MIR-3HG alone or in combination with miR-498 inhibitor or PC-EP300 were subcutaneously injected into mice. The levels of miR-498, EP300 and Ki67 in tumor tissue were measured via reverse transcription-quantitative PCR or western blotting. MIR9-3HG knockdown inhibited the proliferation of cervical cancer cells, whilst promoting apoptosis. MIR9-3HG sponged miR-498 and inhibited its expression. Additionally, miR-498 interacted with EP300 and inhibited its expression. Transfection with miR-498 inhibitor significantly decreased apoptosis levels; this effect was abolished following EP300 silencing in vitro. In vivo, both miR-498 inhibition and EP300 overexpression reversed the inhibition of tumor growth mediated by MIR-3HG knockdown. MIR9-3HG promoted the proliferation cervical cancer cells via EP300 and miR-498. These in vitro and in vivo findings demonstrate the regulatory role of the MIR9-3HG/miR-498/EP300 axis in cervical cancer cell growth. Thus, the present study identified novel molecular targets for the diagnosis and treatment of cervical cancer and provided new insight into the pathogenesis of cervical cancer.