Abstract:
Cervical cancer (CC) is the primary cause of female cancer fatalities in low-middle-income
countries (LMICs). Persistent infections from the human papillomavirus (HPV) can result in cervical
cancer. However, numerous different factors influence the development and progression of
cervical cancer. Transcriptomic knowledge of the mechanisms with which HPV causes cervical
cancer pathogenesis is growing. Nonetheless, there is an existing gap hindering the development of
therapeutic approaches and the improvement of patient outcomes. Alternative splicing allows for the
production of numerous RNA transcripts and protein isoforms from a single gene, increasing the
transcriptome and protein diversity in eukaryotes. Cancer cells exhibit astounding transcriptome
modifications by expressing cancer-specific splicing isoforms. High-risk HPV uses cellular alternative
splicing events to produce viral and host splice variants and proteins that drive cancer progression
or contribute to distinct cancer hallmarks. Understanding how viruses utilize alternative splicing
to drive pathogenesis and tumorigenesis is essential. Although research into the role of miRNAs in
tumorigenesis is advancing, the function of other non-coding RNAs, including lncRNA and circRNA,
has been understudied. Through their interaction with mRNA, non-coding RNAs form a network
of competing endogenous RNAs (ceRNAs), which regulate gene expression and promote cervical
cancer development and advancement. The dysregulated expression of non-coding RNAs is an
understudied and tangled process that promotes cervical cancer development. This review will
present the role of aberrant alternative splicing and immunosuppression events in HPV-mediated
cervical tumorigenesis, and ceRNA network regulation in cervical cancer pathogenesis will also be
discussed. Furthermore, the therapeutic potential of splicing disruptor drugs in cervical cancer will
be deliberated.
