Evaluation of The Anti-Cancer Effect of XBP۱s-Decoy Oligodeoxynucleotide in HCC

Objective: Hepatocellular carcinoma (HCC) is one of the mos tfrequent tumors in humans. X-box binding protein ۱ (XBP۱)is a transcription factor (TF) involved in the unfolded proteinresponse, a cell's adaptive response and defense mechanism tosurvive in severe environments. A growing number of s tudiesdemons trate that XBP۱s is commonly cons titutively activatedin a variety of cancers, including HCC, making it a promisingmolecular target for cancer therapy. Transcription factor decoysoligodeoxynucleotides (TFD) are a new class of oligonucleotide-based molecular therapeutics that are short, double-s trandedDNA. TFD binds to the DNA binding site of a specific genein a target TF and suppresses TF activity as well as gene expression.In the current s tudy, we aimed to reduce the cancerousphenotype in HCC cell lines by treatment of cells with TFD.Materials and Methods: We transfected HCC cells withXBP۱s-decoy ODN, which selectively blocks over-activatedXBP۱s, and assessed cellular migratory ability by wound healingassay. Due to the identified viability potent of HCC cells,cell counting assays were performed. For more evaluation, thelevels of XBP۱s-regulated genes such as BAX, MYC, CYCLIN-D۱, MMP-۹, and CDH۱, which are involved in cell apoptosis,cell cycle, invasion, and migration, were analyzed byquantitative real-time polymerase chain reaction (qRT-PCR).Results: Transfection of HCC cells resulted in significantdown-regulation of MYC, CYCLIN-D۱, MMP-۹, and upregulationof CDH۱ and BAX at transcription levels. Also, theevaluation of cell counting and wound healing assay sugges tedthat transfection of XBP۱s-decoy could reduce cell viabilityand migration capacity of HCC cells as well.Conclusion: This idea shows that transfection of XBP۱s-decoyODN can decrease migration and cell viability. This inhibitoryeffect is accompanied by a reduction and acceleration of ourinteres t genes.

کلیدواژه ها:

Hepatocellular Carcinoma ، X-Box Binding Protein ۱(XBP۱) ، Transcription Factor Decoys Oligodeoxynucleotides ، XBP۱s-Decoy ODN