Abstract
BackgroundKaryopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. Yet its role in colon cancer is poorly characterized. We sought to clarify the clinical significance of its dysregulated expression in human colon tumor specimens.MethodsWe evaluated KPNA2 mRNA and protein expression by real-time polymerase chain reaction and Western blotting in 40 primary colon cancer tissues and paired adjacent normal colon mucosa specimens. KPNA2 protein expression in colon tissue microarray of tumor and normal tissue specimens and lymph node metastasis specimens obtained from 195 colon cancer patients were analyzed immunohistochemically. The effect of KPNA2 knockdown on carcinogenesis potential of human colon cancer cells was determined using Cell Counting Kit-8 (CCK8), colony formation, cell migration, and tumorigenesis in nude mice.ResultsKPNA2 was expressed at higher levels in colon tumors and lymph node metastasis specimens than in normal tissues. Patients with KPNA2-positive tumors were significantly correlated with the American Joint Committee on Cancer (AJCC) stage (p = 0.01), T-classification (p = 0.018), regional lymph node metastasis (p = 0.025), distant metastasis (p = 0.014), and differentiated degree (p = 0.001). KPNA2 was shown to be an independent prognostic indicator of disease-free survival (HR 1.681; 95 % CI: 1.170–2.416; p = 0.005) and overall survival (HR 2.770; 95 % CI: 1.314–5.837; p = 0.007) for patients with colon cancer. Knockdown of KPNA2 expression inhibited colon cancer cell proliferation, colony formation, and migration.ConclusionKPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer.
Highlights
Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis
KPNA2 expression is significantly upregulated in human colon cancer We analyzed 40 paired colon cancer tissues and its adjacent normal tissues to investigate the mRNA expression pattern of KPNA2
Correlation between KPNA2 overexpression and colon cancer clinicopathologic parameters Immunolocalization of KPNA2 protein in the 195 primary colon tumors, as well as paired normal colon mucosa and 66 lymph node metastasis specimens in TMA
Summary
Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. In China, the incidence of colon cancer is increasing rapidly [1]. Both environmental (diet) and genetic factors play key roles in its etiology. It was important to Tumorigenesis and tumor progression are associated with dysfunction of the nuclear transport machinery at the level of import and export receptors (karyopherins) [3]. Aberrant expression of nuclear transport factors may cause altered, mutation-independent, subcellular localization of oncogene or tumor suppressors. Karyopherins act as carrier proteins between the cytoplasm and the nucleus. They mediate the shuttling of macromolecules larger than about 40 kDa, termed nucleocytoplasmic transport [4]
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