Application of XBP1s Decoy Oligodeoxynucleotide Attenuates Cancerous Phenotype in Huh-7 Hepatocellular Carcinoma Cells

Objective: The spliced form of X-box binding protein 1 (XBP1s) is a key transcription factor in the unfolded proteinresponse (UPR), an adaptive mechanism for cell survival. Many studies demonstrated the induced expression ofXBP1s in various cancers, including hepatocellular carcinoma (HCC). Such upregulated expression is linked to anenhancement of cell proliferation, migration, and improvement of the survival rate. In this study, we aimed to assess thetherapeutic potential of targeting XBP1s, by specific decoy oligodeoxynucleotide (ODN) and evaluated the cancerousphenotypes in Huh-7 cells.Materials and Methods: In this experimental study, we transfected Huh-7 cells with XBP1s decoy oligonucleotide(ODN). Subsequently, we assess some cellular features, including viability, migration capacity, proliferation potential,and apoptosis. Therefore, various techniques included wound healing test, BrdU, and annexin/PI assays. Additionally,the colony formation capacity was evaluated. The mRNA expression levels of BAX, BCL-2, c-MYC, CCND1, MMP-9,CDH1, and CD133 were quantified by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: Transfection of Huh-7 cells by XBP1s decoy ODN led to significant down-regulation of c-Myc, CCND1,MMP-9, BCL-2 and CD133 and up-regulation of CDH1 and BAX transcriptional expressions in comparison with thevehicle group. Our results also demonstrated that transfection of XBP1s-decoy reduced HCC cell viability, proliferation,migration capacity as well as colonization ability in comparison with the vehicle group.Conclusion: These findings proposed the potential application of XBP1s-decoy ODN to reduce cancerous phenotypessuch as cell proliferation, cell migration and apoptosis induction in the Huh-7 cell line. More experiments on other celllines and primary cells could validate our results.