Abstract
Coiled-coil domain containing (CCDC) family members enhance tumor cell proliferation, and high CCDC protein levels correlate with unfavorable prognoses. Limited research demonstrated that CCDC106 may promote the degradation of p53/TP53 protein and inhibit its transactivity. The present study demonstrated that CCDC106 expression correlates with advanced TNM stage (P = 0.008), positive regional lymph node metastasis (P < 0.001), and poor overall survival (P < 0.001) in 183 non-small cell lung cancer cases. A549 and H1299 cells were selected as representative of CCDC106-low and CCDC106-high expressing cell lines, respectively. CCDC106 overexpression promoted A549 cell proliferation and xenograft tumor growth in nude mice, while siRNA-mediated CCDC106 knockdown inhibited H1299 cell proliferation. CCDC106 promoted AKT phosphorylation and upregulated the cell cycle-regulating proteins Cyclin A2 and Cyclin B1. Cell proliferation promoted by CCDC106 via Cyclin A2 and Cyclin B1 was rescued by treatment with the AKT inhibitor, LY294002. Our studies revealed that CCDC106 is associated with non-small cell lung cancer progression and unfavorable prognosis. CCDC106 enhanced Cyclin A2 and Cyclin B1 expression and promoted A549 and H1299 cell proliferation, which depended on AKT signaling. These results suggest that CCDC106 may be a novel target for lung cancer treatment.
Highlights
Coiled-coil domain containing 106 protein (CCDC106), previously called HSU79303 [1], may promote p53 degradation through direct interaction in Hela cells [2]
We found that CCDC106 overexpression in non-small cell lung cancer (NSCLC) tissues correlated with advanced TNM stage, positive regional lymph node metastasis, and poor overall survival
We found that CCDC106 was highly expressed in the cytoplasm of NSCLC tumor cells and lung cancer cell lines
Summary
Coiled-coil domain containing 106 protein (CCDC106), previously called HSU79303 [1], may promote p53 degradation through direct interaction in Hela cells [2]. TP53 is a tumor suppressor and is responsible for DNA damage and cell cycle regulation [3,4,5,6]. We hypothesized that CCDC106 is involved in human cancer progression and cell cycle regulation. Previous studies indicated that other CCDC family members enhance tumor cell proliferation, and high protein levels correlate with unfavorable prognosis [9]. We explored CCDC106 expression patterns and subcellular distributions in both lung cancer tissues and cell lines. We found that CCDC106 overexpression in non-small cell lung cancer (NSCLC) tissues correlated with advanced TNM stage, positive regional lymph node metastasis, and poor overall survival. We found that CCDC106 increased Cyclin A2 and Cyclin B1 expression, promoting cell proliferation in vitro and in vivo through AKT pathway activation
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