Background: Colorectal cancer is one of the three most common cancers worldwide. Altered TGF-β signaling pathway in colorectal cancer is associated with metastasis and poor prognosis. It is also involved in epithelial-to-mesenchymal transition (EMT), which is essential in progression and metastasis. This study aims to investigate the role of transgelin (TAGLN) and high-mobility group AT-hook 2 (HMGA2) in the progression of colon cancer.
Methods: HT29 and HCT116 cells were treated with TGF-β, and the effects of inhibition of TAGLN  and overexpression of HMGA2 on TGF-β treated cell on cell migration and invasion, expression of EMT markers, including E-cadherin, vimentin and fibronectin were detected as well as MMP2 and MMP9, which are critical in cancer cell metastasis. The interaction of TAGLN and HMGA2 was also investigated by using co-immunoprecipitation. The function of TAGLN  in tumor metastasis and growth was investigated in vivo.
Results: We found that TGF-β could significantly promote the migration of HT29 and HCT116 cells, as well as TAGLN  protein expression and nucleus translocation, while inhibition of TAGLN  could effectively reverse the effects of TGF-β on HT29 and HCT116 cells, which was observed in terms of decreased cell migration and invasion. Knockdown of TAGLN  could also rescue TGF-β-induced loss of E-cadherin, and decreased TGF-β-induced vimentin and fibronectin expression; the elevation of MMP9 and MMP2 was also reversed by inhibition of TAGLN . Further investigation confirmed the interaction of HMGA2 and TAGLN , as overexpression of HMGA2 restores the effects of TGF-β on HT29 cells, which were attenuated by TAGLN  inhibition both in vitro and in vivo.
Conclusion: Overall, our study revealed that interaction between TAGLN  and HMGA2 was involved in TGF-β-induced cell migration and promotion of colon cancer cells, suggesting that HMGA2 and TAGLN  are potential molecular targets to prevent colon cancer progression.
Keywords: HMGA2, colorectal cancer, TGF-β, TAGLN