Downregulation of LAMB3 altered the carcinogenic properties of human
papillomavirus 16 positive cervical cancer cells
Abstract
Nearly all cervical cancer cases are infected with high risk (HR)-HPV
types, with HR-HPV16 accounting for more than 50%. The mechanism of
cervical cell transformation is related to the powerful action of viral
E6 and E7 oncoproteins. Transcriptomic sequencing (RNA-seq) data from
HPV16 positive and HPV negative cervical cancer cell lines were utilized
to identify upregulated genes and their associated pathways. There were
593 overlapping upregulated genes (fold change >4) found in
HPV16 positive cell lines. According to gene ontology analysis, these
genes were predominantly expressed in extracellular region and plasma
membrane that play a role in protein binding and cell adhesion molecule
binding, leading to response to stimulus and tissue development. KEGG
pathway analysis showed that the most significant pathways were
metabolic pathways, pathway in cancer, MAPK signaling pathway, and
PI3K-AKT signaling pathway. The laminin subunit beta-3 (LAMB3) gene was
chosen for functional analysis. LAMB3 knockdown decreased cell
migration, invasion, anchorage dependent- and anchorage independent-cell
growth and increased number of apoptotic cells of HPV16 positive
cervical cancer cells. These effects were linked to a decrease in
protein levels involved in the PI3K-AKT signaling pathway and increased
p53 protein. This study demonstrated that LAMB3 could promote cervical
cancer cell migration, invasion and survival.