Abstract:
Cervical cancer is one of the most prevalent types of gynaecological malignancy in women
around the globe. Along with the HPV infections several genetic players are also involved
in the onset and progression of cervical cancer. KPCE is an isoform in the novel-KPC
subfamily of AGC-kinases that plays a crucial role in the development of different cancers.
Various studies have shown that genetic variants in KPCE are associated with several
ailments including cancers as a result of their altered structural and functional profile. Till
this date, no data has been published that has elucidated the impact of KPCE genetic
variants in association with cervical cancer. Therefore, the objectives of this study are to
identify novel pathogenic genetic variants in KPCE and explore their impact on protein
structure, function, stabilization, and molecular interactions with one of Its target proteins
which is Smad3 in this study. Moreover, this study also intended to explore the role of
those variants with cervical cancer through genotype analysis. This study has revealed that
KPCE genetic variants rs1553369874 and rs1345511001 in the regulatory C2-like domain
have an association with the risk of cervical cancer development. Interaction dynamics
analysis has proved that KPCE variant structures and Smad3 interact in an aberrant manner
compared to native KPCE – Smad3 interaction, which might lead to the activation of
Warburg`s effect and angiogenesis. Data obtained from this research can be potentially
used for the development of novel therapeutic targets for better treatment options against
cervical cancer as well as the novel biomarkers for early diagnosis and better prognosis
