SNORD6 promotes cervical cancer progression by accelerating E6-mediated p53 degradation

Abstract

AbstractSmall nucleolar RNAs (snoRNAs) are a class of non-coding RNAs widely distributed in eukaryotic nucleoli. In recent years, studies have revealed that snoRNAs can also participate in the occurrence and development of malignant tumors through different pathways. Cervical cancer is one of the most common malignant tumors of the female reproductive system, and the high-risk HPV virus infection is its main pathogenic mechanism. However, the outcomes in different patients with malignant tumors vary, indicating that other factors might affect the pathogenic process of cervical cancer. In this study, we screened the poor prognosis indicator SNORD6 from the TCGA database to find the snoRNA that affects the disease outcome during the pathogenesis of cervical cancer. We discovered that SNORD6 expression in cervical cancer tissues was higher than that in normal cervical tissues. Cell phenotype experiments revealed that the knockdown of SNORD6 retarded cell proliferation and plate clone formation. Furthermore, G1-S phase cell cycle arrest was induced, DNA synthesis was decreased, cell migration and invasion were reduced, while the level of apoptosis increased, whereas the opposite results were obtained after SNORD6 overexpression. Moreover, after intratumoral injection of ASO-SNORD6, the tumor growth rate slowed down, and the tumor volume decreased compared with the control group. In the mechanism study, we found that SNORD6 concurrently acted as a binding “hub” to promote the formation of the tumor suppressor protein p53 degradation complex E6-E6AP-p53. This reaction enhanced the ubiquitination and degradation of p53, thus influenced the regulation of p53 activities in the cell cycle and apoptosis. This study preliminarily clarified the biological role and specific mechanism of SNORD6 in the occurrence of cervical cancer, broadening the basic theoretical research of ovarian cancer and may provide a new perspective on the diagnosis and treatment of cervical cancer.