Anticancer activity of HMGA1 promoter targeting triplex forming oligonucleotide in HeLa cell line

High mobility group protein Al (HMGA1) acts as an architectural transcription factor and regulates transcription of various genes. Upregulation of HMGA1 has been described in a large number of human malignancies and serves as a 'tumor marker'. Due to its role in neoplastic transformation and tumor progression, hmgal is considered as a promising therapeutic target. In the present study, we investigated the interaction of triplex forming oligonucleotide (TFO) of 18 bps targeted to hmgal promoter (-1917 to 1940) and its influence on the expression of HMGA1 in HeLa cells. Stability of DNA triplex was characterized using various biophysical and thermodynamic methods and was confirmed by gel retardation assay using gamma-P-32 [ATP]. Treatment of HeLa cells with hmgal specific TFO significantly downregulated HMGA1 expression at mRNA, protein levels (similar to 48%) and inhibited cell proliferation as investigated by RT-PCR, Western blot and Flow cytometiy. The findings of the study suggest that TFO-mediated inhibition of hmgal expression can be a promising strategy for modulation of gene expression and for inhibition of cancer cell proliferation. Moreover, DNA triplex-based therapeutic approaches hold promise in combating cancers associated with HMGA1 overexpression.