Truncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a TGF-β Context Dependent Manner
Author | Narges Rahmanian |
Author | Parastoo Tarighi |
Author | Mehdi Gharghabi |
Author | Maryam Torshabi |
Author | Ghorban Ali Tarfiei |
Author | Taiebeh Mohammadi Farsani |
Author | Seyed Naser Ostad |
Author | Mohammad Hossein Ghahremani |
Issued Date | 2017-07-31 |
Abstract | The Runt related transcription factors (RUNX) are recognized as key players in suppressing or promoting tumor growth. RUNX3, a member of this family, is known as a tumor suppressor in many types of cancers, although such a paradigm was challenged by some researchers. The TGF-β pathway governs major upstream signals to activate RUNX3. RUNX3 protein consists of several regions and domains. The Runt domain is a conserved DNA binding domain and is considered as the main part of RUNX proteins. Herein, we compared the effects of Runt domains and full-Runx3 in cell viability by designing two constructs of Runx3, including N-terminal region and Runt domain. We investigated the effect of full-Runx3, N-t, and RD on growth inhibition in AGS, MCF-7, A549, and HEK293 cell lines which are different in TGF-β sensitivity, in the absence and presence of TGF-β. The full length RUNX3 did not notably inhibit growth of these cell lines while, the N-t and RD truncates showed different trends in these cell lines. Cell proliferation in the TGF-β impaired context cell lines (AGS and MCF-7) significantly decrease while in the A549 significantly increase. On the other hand, transfection of N-t and RD did not considerably affect the cell proliferation in the HEK293.Our results show that full-lenght RUNX3 did not affect the cell viability. Conversely, the N-t and RD constructs significantly changed cell proliferation. Therefore, therapeutic potentials for these truncated proteins are suggested in tumors with RUNX proteins dysfunction, even in the TGF-β impair context. |
DOI | https://doi.org/10.22037/ijpr.2017.2105 |
Keyword | Runt |
Keyword | Cancer |
Keyword | TGF-β |
Keyword | Domain Analysis |
Keyword | Apoptosis |
Publisher | Brieflands |
Title | Truncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a TGF-β Context Dependent Manner |
Type | Original Article_imported |
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