Lung Cancer |

Oncogenic Function of Psf3 in Non-small Cell Lung Cancer FREE TO VIEW

Yoshimasa Maniwa, MD
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Kobe University Graduate School of Medicine, Kobe, Japan

Chest. 2015;148(4_MeetingAbstracts):549A. doi:10.1378/chest.2279200
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SESSION TITLE: Lung Cancer Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM

PURPOSE: We previously found that increased Psf3 expression was strongly associated with poor survival in lung adenocarcinoma. Herein, we investigated the role of Psf3 expression in non-small cell lung cancer (NSCLC).

METHODS: We verified Psf3 expression in human NSCLC tissues (12 patients) and cell lines. We assessed whether Psf3 expressions in cancer cells functioned as the CMG complex. Moreover, we knocked down Psf3 expression by using RNAi, which allowed us to assess the role of Psf3 expression.

RESULTS: Immunohistochemical analysis revealed that increased Psf3 expression was associated with poor degrees of differentiation in squamous cell carcinoma, as well as adenocarcinoma. We employed A549 and EBC1 NSCLC cell lines, which showed strong Psf3 expression by western blotting analysis. A proximal ligation assay showed interactions between Psf3 and other CMG components (such as Mcm2 and Cdc45) in both NSCLC specimens and cell lines, indicating that Psf3 acted as the CMG complex, which could lead to excessive proliferation. Psf3 knockdown inhibited the proliferation of both cell lines by delaying the S phase.

CONCLUSIONS: In conclusion, Psf3 expressions were strongly correlated with tumor grade in NSCLC. Over-expressed Psf3, which acts as a CMG complex, is crucial for cancer cell proliferation in human lung cancer. Psf3 might function as oncogenic molecle with its partners in NSCLC.

CLINICAL IMPLICATIONS: Psf3 is a member of GINS complex, which associates with the mini-chromosome maintenance (Mcm) proteins Mcm2-7 and with Cdc45 to form CMG complex. The CMG complex is known to regulate both the initiation and the progression of DNA replication. Our investigation of surgically resected specimens from patients with non-small-cell lung cancer (NSCLC) revealed that Psf3 expression was strongly correlated with tumor grade in NSCLC. Moreover, Psf3 acted as the CMG complex, which could lead to excessive proliferation. These findings provide clues regarding the role of Psf3 in NSCLC, and could yield novel molecular-targeted treatment strategies aimed at inhibiting the pathways that lead to the proliferation and progression of NSCLC.

DISCLOSURE: The following authors have nothing to disclose: Yoshimasa Maniwa

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