Cervical cancer (CC) remains one of the most common female malignancies, with higher incidence and mortality rates. more than 99% of cervical cancers are associated with persistent infection with high-risk human papillomavirus. In view of the growing evidence that HPV 16 E6 and E7, two key oncoproteins encoded by HPV 16, regulate the expression of many other multifunctional genes and downstream effectors that contribute to the development of cervical cancer. Herein, we undertook a comprehensive effort into how HPV16 E6, E7 oncogenes affect the progression of CC cells. Previous studies have shown that ICAT expression was significantly increased in cervical cancer and had a pro-cancer effect. We observed that knockdown of HPV16 E6, E7 expression in SiHa and CasKi cells resulted in significant inhibition of ICAT expression and upregulation of miR-23b-3p expression. Besides, dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p, and negatively modulated by miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of CC cells, such as migration, invasion and EMT. The overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16-positive CC cells. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CaSki cells. Collectively, our findings uncover that HPV16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16-positive CC pathogenesis, which may serve as a promising therapeutic target for HPV16-associated cervical cancer.

Regulator of chromatin condensation 1 (RCC1) is the major guanine nucleotide exchange factor of RAN GTPase, which plays a key role in various biological processes such as cell cycle and DNA damage repair. Small nucleolar RNA host gene 3 (SNHG3) and SNHG12 are long-stranded non-coding RNAs (lncRNAs) and are located on chromatin very close to the sequence of RCC1. Many studies have shown that they are aberrantly expressed in tumor tissues and can affect the proliferation and viability of cancer cells. Although the effects of RCC1/SNHG3/SNHG12 on cellular activity have been reported, respectively, their overall analysis on the pan-cancer level has not been performed. Here, we performed a comprehensive analysis of RCC1/SNHG3/SNHG12 in 33 cancers through the Cancer Genome Atlas and Gene Expression Database. The results showed that RCC1/SNHG3/SNHG12 were highly expressed in a variety of tumor tissues compared to normal tissues. The expression of RCC1/SNHG3/SNHG12 in BRCA, LGG and LIHC was associated with TP53 mutations. In addition, RCC1/SNHG3/SNHG12 expression was closely associated with the prognosis of patients with multiple tumors. Immunocorrelation analysis indicated that RCC1/SNHG3/SNHG12 showed a correlation with multiple immune cell infiltration. The results of enrichment analysis suggested that RCC1/SNHG3/SNHG12 was involved in the regulation of cell cycle, apoptosis and other pathways. We found that these effects were mainly mediated by RCC1, while the trend of SNHG3/SNHG12 regulation was also consistent with RCC1. We refer to this phenomenon as "homodomain effect". These findings provide new and comprehensive insights into the role of RCC1/SNHG3/SNHG12 in tumor development and show their potential as clinical monitoring and therapy.

Background: Human papillomavirus (HPV) 16 plays a crucial role in cervical cancer (CC) development. Previous study reported that inhibitor of β-catenin and TCF (ICAT) is upregulated in CC and promotes cervical tumor progression. Herein, we aimed to investigate the underlying molecular mechanism that HPV16 regulates the expression of ICAT and promotes the CC development. Methods: The expressions of HPV 16 E6, E7 and ICAT were modulated by small interfering RNA and recombinant adenovirus, respectively. qRT-PCR was conducted to detect the mRNA expression of HPV 16 E6, E7, ICAT and miR-23b-3p in SiHa and CasKi cells. Bioinformatics analysis was utilized to predict the potential miRNAs that could bind to the ICAT 3′ untranslated region. Then, the dual luciferase reporter assay was used to confirm that. Cell proliferation ability was detected by CCK-8 assay. Wound healing and Transwell assays were used to observe migration and invasion abilities. Protein expressions were measured with western blot. Results: Results revealed that after knocking down of HPV16 E6, E7, the expression of ICAT decreased, but the expression of miR-23b-3p increased. Besides, miR-23b-3p negatively modulated ICAT expression in HPV16 positive CC cells. Dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of SiHa and CasKi cells, such as migration, invasion and EMT. Importantly, the overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16 positive cervical cancer cell. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CasKi cells.Conclusions: Our study demonstrates that HPV 16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16 positive CC pathogenesis, which may serve as a promising therapy target for HPV 16-associated cervical cancer.