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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Presentations: 1
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
13P - The identification of binding targets for pro-metastatic protein NIFK in lung cancer (ID 325)
12:30 - 13:00 | Presenting Author(s): T.C. Lin
We previously identified nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) as a poor prognostic marker in lung cancer. Furthermore, NIFK overexpression promotes cancer metastasis via decreasing casein kinase 1α (CK1α) expression, a suppressor of pro-metastatic TCF4/β-catenin signaling. We further observe the axis is induced by the downregulation of a novel transcription factor RUNX1. However, the interplay between NIFK, CK1α and RUNX1 remains largely unknown. In this study, we aim to unravel the interactive mechanism of the signaling axis NIFK/RUNX1/CK1α, and to characterize its potential clinical value in cancer patient cohort.
NIFK is pointed out to possess RNA binding function via the RNA Recognition Motif (RRM). RNA immunoprecipitation assay was performed using specific NIFK antibody in lung cancer PC13 and A549 cells after NIFK overexpression. RNA targets were analyzed by RT-PCR and Next Generation Sequencing (NGS). In addition, relative NIFK, RUNX1 and CK1α expression and its association with patient survival outcome were investigated in lung cancer cohorts.
We observe the increase in amount of RNA binding targets after NIFK overexpression respectively in PC13 and A549 cells as comparing with the control. Moreover, NIFK appears to bind with RUNX1 RNA but not CK1α suggesting it is the initial step of NIFK-mediated TCF4/β-catenin signaling regulation. NIFK also leads to RUNX1 RNA instability of which mechanism remains to be explored. RUNX1 is observed to associate with good prognosis in lung cancer datasets (jacob-00182-CANDF and GSE13213). In addition, relative expression of the axis is further revealed in lung cancer cohort.
We first show the interactive mechanism of pro-metastatic molecule NIFK in regulating TCF4/β-catenin signaling, which might contribute to therapeutic target design for lung cancer patients.
Clinical trial identification:
Legal entity responsible for the study:
Chang Gung Memorial Hospital
Ministry of Science and Technology, Taiwan
All authors have declared no conflicts of interest.