Comprehensive analysis of ceRNA networks in HPV16-and HPV18-mediated cervical cancers reveals XIST as a pivotal competing endogenous RNA

Cervical cancer (CC) is one of the most common cancers in women worldwide, being closely related to high-risk human papillomavirus (HR-HPVs). After a particular HR-HPV infects a cervical cell, transcriptional changes in the host cell are expected, including the regulation of lncRNAs, miRNAs, and mRNAs. Such transcripts may work independently or integrated in complex molecular networks - as in competing endogenous RNA (ceRNA) networks. In our research, we gathered transcriptome data from samples of HPV16/HPV18 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), from The Cancer Genome Atlas (TCGA) project. Using GDCRNATools, we identified ceRNA networks that differentiate HPV16- from HPV18-mediated CESC. For HPV16-CESC, three lncRNA-mRNA co-expressed pairs were reported, all led by the X-inactive specific transcript (XIST): XIST vertical bar DLG5, XIST vertical bar LGR4, and XIST vertical bar ZNF81. The XIST vertical bar LGR4 and XIST vertical bar ZNF81 pairs shared 11 miRNAs, suggesting an increased impact on their final biological effect. XIST also stood out as an important lncRNA in HPV18-CESC, leading 35 of the 42 co-expressed pairs. Some mRNAs, such as ADAM9 and SLC38A2, emerged as important players in the ceRNA regulatory networks due to sharing a considerable amount of miRNAs with XIST. Furthermore, some XIST-associated axes, namely XIST vertical bar miR-23a-3p vertical bar LGR4 and XIST vertical bar miR-30b-5p or miR-30c5p or miR-30e-5p I ADAM9, had a significant impact on the overall survival of HPV16- and HPV18-CESC patients, respectively. Together, these data suggest that XIST has an important role in HPV-mediated tumorigenesis, which may implicate different molecular signatures between HPV16 and HPV18-associated tumors.

Automated summary

Research suggests that XIST plays a crucial role in HPV-mediated cervical cancer, potentially implicating different molecular signatures between HPV16 and HPV18-associated tumors. XIST regulates cellular functions by co-expressing with multiple lncRNA-mRNA pairs and sharing miRNAs, impacting biological effects.