Association of overexpressed karyopherin alpha 2 with poor survival and its contribution to interleukin-1-induced matrix metalloproteinase expression in oral cancer

作者：Wang Chun I; Yu Chia Jung; Huang Yenlin; Yi Jui Shan; Cheng Hsing Wen; Kao Huang Kai; Lao William Wei Kai; Chang Kai Ping^*

来源：Head and Neck-Journal for the Sciences and Specialties of the Head and Neck, 2018, 40(8): 1719-1733.

DOI：10.1002/hed.25145

• interleukin-1 (IL-1)
• invasiveness
• karyopherin alpha 2 (KPNA2)
• matrix metalloproteinase (MMP)
• oral cavity squamous cell carcinoma (SCC)
• survival

BackgroundThe purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression.
MethodsThe KPNA2 expressions were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2-knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real-time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor-kappa B (NF-B).
ResultsThe KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease-specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)-1-induced nuclear import of NF-B and MMP (MMP-1, MMP-3, and MMP-9) transcription.
ConclusionThe KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP-mediated metastasis.

• 出版日期2018-8
• 单位长春大学