Overexpression of HURP mRNA in head and neck carcinoma and association with in�vitro response to vinorelbine

Abstract

HURP gene encodes the hepatoma upregulated protein (HURP), a microtubule associated protein regulating mitotic spindle dynamics, which promotes chromosomal congression and alignment during mitosis, with a potential role in tumorigenesis. In the present study, HURP mRNA expression was investigated by reverse transcription-quantitative PCR in oropharyngeal squamous cell carcinoma (OPSCC). Primary OPSCC tumors from 107 patients and 48 adjacent normal tissues, as well as 12 respiratory tract cancer cell lines (9 head and neck squamous cell carcinoma, 2 lung cancer and 1 normal bronchial) were utilised in the present study. mRNA expression levels of HURP were higher in malignant OPSCC tissues compared with in normal mucosa (P<1x10-5) and significantly associated with sex and smoking status (P<0.0001). Vinorelbine in vitro toxicity at half-maximal inhibitory concentration (IC 50) was measured in the 11 cancer cell lines using an MTT assay. Sensitivity to vinorelbine was significantly correlated with HURP expression (r=0.636; P=0.035). The data indicated that HURP overexpression is frequent in OPSCC tissues and associated with smoking. The correlation between HURP mRNA expression and vinorelbine in vitro response suggests that HURP is a potential modulator of vinorelbine response; therefore, it should be explored for its possible predictive value for the efficiency of vinorelbine treatment in this type of cancer.

Potential effects of miR‑146 expression in relation to malondialdehyde as a biomarker for oxidative damage in patients with breast cancer

“…When biomolecule peroxidation occurs, a number of carcinogenic and mutagenic factors are produced (25). Exploring the potential role of ectopic gene expression in patients with cancer has recently attracted the research interests of the authors (26)(27)(28)(29). Despite the fact that a higher expression of miR-146 is associated with increased levels of MDA in normal tissues (30)(31)(32), to date, at least to the best of our knowledge, there are no reports available suggesting a similar association in malignant tissues.…”

DLGAP5 knockdown inactivates the Wnt/β‐catenin signal to repress endometrial cancer cell malignant activities

“…Human discs large‐associated protein 5 (DLGAP5) is encoded by DLGAP5 gene, located at chromosome 14q22.3 10 . DLGAP5 is a RanGTP‐dependent microtubule‐associated protein involved in regulating spindle assembly, kinetochore fibers stabilization, and chromosomal congression, alignment and segregation during mitosis 11,12 .…”

Molecular interplay between HURP and Kif18A in mitotic spindle regulation

“…When HURP is depleted, Kif18A likely remains in an auto-inhibited state that limits the number of landing events that result in processive motility. On the other hand, when HURP is overexpressed in pathological states of the cell 12,[44][45][46] , it could saturate the microtubule surface and block efficient Kif18A walking.…”

“…When HURP is depleted, Kif18A likely remains in an auto-inhibited state that limits the number of landing events that result in processive motility. On the other hand, when HURP is overexpressed in pathological states of the cell 12,44–46 , it could saturate the microtubule surface and block efficient Kif18A walking. Both of these situations would lead to inefficient accumulation of Kif18A at the kinetochore-proximal end, promoting defects in chromosome congression during mitosis (Figure 6 A).…”