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2.
Int J Oncol ; 57(1): 277-288, 2020 07.
Article in English | MEDLINE | ID: mdl-32467984

ABSTRACT

The aim of the present study was to identify novel prognostic biomarkers and therapeutic targets for breast cancer; thus, genes that are frequently overexpressed in several types of breast cancer were screened. Kinesin family member 20A (KIF20A) was identified as a candidate molecule during this process. Immunohistochemical staining performed using tissue microarrays from 257 samples of different breast cancer subtypes revealed that KIF20A was expressed in 195 (75.9%) of these samples, whereas it was seldom expressed in normal breast tissue. KIF20A protein was expressed in all types of breast cancer observed. However, it was more frequently expressed in human epidermal growth factor receptor 2 (HER2)­positive and triple­negative breast cancer than in the luminal type. Moreover, KIF20A expression was significantly associated with the poor prognosis of patients with breast cancer. A multivariate analysis indicated that KIF20A expression was an independent prognostic factor for patients with breast cancer. The suppression of endogenous KIF20A expression using small interfering ribonucleic acids or via treatment with paprotrain, a selective inhibitor of KIF20A, significantly inhibited breast cancer cell growth through cell cycle arrest at the G2/M phase and subsequent mitotic cell death. These results suggest that KIF20A is a candidate prognostic biomarker and therapeutic target for different types of breast cancer.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Kinesins/metabolism , Aged , Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , Kinesins/antagonists & inhibitors , Kinesins/genetics , Middle Aged , Prognosis
3.
Int J Oncol ; 52(1): 155-165, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29115586

ABSTRACT

Oral cancer has a high mortality rate, and its incidence is increasing gradually worldwide. As the effectiveness of standard treatments is still limited, the development of new therapeutic strategies is eagerly awaited. Kinesin family member 11 (KIF11) is a motor protein required for establishing a bipolar spindle in cell division. The role of KIF11 in oral cancer is unclear. Therefore, the present study aimed to assess the role of KIF11 in oral cancer and evaluate its role as a prognostic biomarker and therapeutic target for treating oral cancer. Immunohistochemical analysis demonstrated that KIF11 was expressed in 64 of 99 (64.6%) oral cancer tissues but not in healthy oral epithelia. Strong KIF11 expression was significantly associated with poor prognosis among oral cancer patients (P=0.034), and multivariate analysis confirmed its independent prognostic value. In addition, inhibition of KIF11 expression by transfection of siRNAs into oral cancer cells or treatment of cells with a KIF11 inhibitor significantly suppressed cell proliferation, probably through G2/M arrest and subsequent induction of apoptosis. These results suggest that KIF11 could be a potential prognostic biomarker and therapeutic target for oral cancer.


Subject(s)
Kinesins/biosynthesis , Mouth Neoplasms/enzymology , Aged , Apoptosis/physiology , Benzamides/pharmacology , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Cell Growth Processes/physiology , Cell Line, Tumor , Chromones/pharmacology , Female , Gene Knockdown Techniques , Humans , Immunohistochemistry , Keratinocytes/enzymology , Kinesins/antagonists & inhibitors , Kinesins/genetics , Male , Middle Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Prognosis , Tissue Array Analysis
4.
Int J Oncol ; 49(4): 1385-93, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27499128

ABSTRACT

Oral cavity carcinoma (OCC) is one of the most common causes of cancer-related death worldwide and has poor clinical outcome after standard therapies. Therefore, new prognostic biomarkers and therapeutic targets for OCC are urgently needed. We selected cell division cycle associated 1 (CDCA1) as a candidate OCC biomarker. Immunohistochemical analysis confirmed that CDCA1 protein was expressed in 67 of 99 OCC tissues (67.7%), but not in healthy oral epithelia. CDCA1 expression was significantly associated with poor prognosis in OCC patients (P=0.0244). Knockdown of CDCA1 by siRNAs significantly increased apoptosis of tumor cells. These data suggest that CDCA1 represents a novel prognostic biomarker and therapeutic target for OCC.


Subject(s)
Biomarkers, Tumor/metabolism , Cell Cycle Proteins/metabolism , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Up-Regulation , Adult , Aged , Aged, 80 and over , Apoptosis , Biomarkers, Tumor/genetics , Cell Cycle Proteins/genetics , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Male , Middle Aged , Molecular Targeted Therapy , Mouth Neoplasms/drug therapy , Mouth Neoplasms/genetics , Prognosis , Survival Analysis
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