Truncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a TGF-β Context Dependent Manner

AuthorNarges Rahmanian
AuthorParastoo Tarighi
AuthorMehdi Gharghabi
AuthorMaryam Torshabi
AuthorGhorban Ali Tarfiei
AuthorTaiebeh Mohammadi Farsani
AuthorSeyed Naser Ostad
AuthorMohammad Hossein Ghahremani
Issued Date2017-07-31
AbstractThe 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.
DOIhttps://doi.org/10.22037/ijpr.2017.2105
KeywordRunt
KeywordCancer
KeywordTGF-β
KeywordDomain Analysis
KeywordApoptosis
PublisherBrieflands
TitleTruncated forms of RUNX3 Unlike Full Length Protein Alter Cell Proliferation in a TGF-β Context Dependent Manner
TypeOriginal Article_imported
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
ijpr-16-1194.pdf
Size:
569.33 KB
Format:
Adobe Portable Document Format
Description:
Article/s PDF