Thematic Excellence Program (Semmelweis University)(2020-4.1.1.-TKP2020) Támogató:
Innovációs és Technológiai Minisztérium
Breast cancer is the third most common type of cancer diagnosed. Cell cycle is a complex
but highly organized and controlled process, in which normal cells sense mitogenic
growth signals that instruct them to enter and progress through their cell cycle.
This process culminates in cell division generating two daughter cells with identical
amounts of genetic material. Uncontrolled proliferation is one of the hallmarks of
cancer. In this study, we analyzed the expression of the cell cycle-related genes
receptor for hyaluronan (HA)-mediated motility (RHAMM), AURKA, TPX2, PLK1, and PLK4
and correlated them with the prognosis in a collective of 3952 breast cancer patients.
A high messenger RNA expression of all studied genes correlated with a poor prognosis.
Stratifying the patients according to the expression of hormonal receptors, we found
that in patients with estrogen and progesterone receptor-positive and human epithelial
growth factor receptor 2-negative tumors, and Luminal A and Luminal B tumors, the
expression of the five analyzed genes correlates with worse survival. qPCR analysis
of a panel of breast cancer cell lines representative of major molecular subtypes
indicated a predominant expression in the luminal subtype. In vitro experiments showed
that radiation influences the expression of the five analyzed genes both in luminal
and triple-negative model cell lines. Functional analysis of MDA-MB-231 cells showed
that small interfering RNA knockdown of PLK4 and TPX2 and pharmacological inhibition
of PLK1 had an impact on the cell cycle and colony formation. Looking for a potential
upstream regulation by microRNAs, we observed a differential expression of RHAMM,
AURKA, TPX2, PLK1, and PLK4 after transfecting the MDA-MB-231 cells with three different
microRNAs. Survival analysis of miR-34c-5p, miR-375, and miR-142-3p showed a different
impact on the prognosis of breast cancer patients. Our study suggests that RHAMM,
AURKA, TPX2, PLK1, and PLK4 can be used as potential targets for treatment or as a
prognostic value in breast cancer patients.
