مقالات پذیرفته شده در ششمین کنگره بین المللی زیست پزشکی
Investigating the Effect of Ni-Thiosemicarbazones complexes on Expression Changes of LncRNA TUG1 in Acute Lymphoblastic Leukemia
Investigating the Effect of Ni-Thiosemicarbazones complexes on Expression Changes of LncRNA TUG1 in Acute Lymphoblastic Leukemia
Neda zahmatkesh,1Mahnaz Eskandari,2Golnaz Asaadi Tehrani,3,*Sina Mirza Ahmadi,4
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran. 2. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran. 4. Assistant professor of Molecular Genetics, Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: leukemia that affects lymphoid progenitor cells in the bone marrow, blood, and extramedullary regions is known as acute lymphoblastic leukemia (ALL). Relapse has a significant impact on survival in ALL. The prognosis has improved and there has been a substantial advancement in ALL treatment over the past couple of decades. In a study of children's ALL outcomes, the Children's Oncology Group found that, between 1990 and 2000, 5-year survival rates rose from 83% to more than 90%. All child age groups have shown this to be true, with the exception of newborns under a year old. Even with these improvements, 20% or so of children with ALL still experience relapses. The term "long non-coding RNAs" (lncRNAs) refers to RNAs that are longer than 200 nucleotides. The importance of lncRNAs in a variety of cellular processes, including proliferation, differentiation, apoptosis, invasion, and chromatin modification, has been demonstrated in an increasing number of studies. In this regard, it has been shown that lncRNAs are dysregulated in human malignancies. TUG1 is a recently discovered oncogenic lncRNA that has been found to exhibit aberrant upregulation in a variety of cancers, including leukemia, hepatocellular carcinoma, bladder cancer, B-cell malignancies, and oesophageal squamous cell carcinoma. TUG1 knockdown has been found to inhibit colony formation, cell invasion, and/or cell proliferation in various malignancies. TUG1 has an interesting downregulated expression pattern in non-small cell lung cancer, indicating a tissue-specific role in carcinogenesis. TUG1 could be used in clinical settings as a prognostic biomarker for malignancies. Leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer, and bladder cancer are only a few of the malignancies that thiosemicarbazones are effective against. The goal of this study was to investigate of Ni-thiosemicarbazones complexes affected the expression of LncRNA TUG1 in the Jurkat E6.1 cell line.
Methods: In this research, appropriate doses of the thiosemicarbazones complexes Ni were prepared according to the IC50 of the drug which consists of 46 and 48µM. The Jurkat E6.1 cell line was treated by Ni 72 hours after cell passage. The expression changes of LncRNA TUG1 and GAPDH as the housekeeping gene were investigated using Real-Time PCR after RNA extraction and cDNA synthesis. Finally, Rest 2002 Software was used to analyze the data, and Excel was used to create diagrams.
Results: The Results of the research showed that after 72 hours of treatment with thiosemicarbazones complexes Ni at 46 and 48µM concentrations, the expression of LncRNA TUG1decreased significantly as compared to the control group. According to the findings, doses of 46 and 48µM of Ni over 72 hours were the optimal concentrations and time for this drug's effect. The expressions of LncRNA TUG1 were 1.968 and 2.369 at the specified concentrations and times.
Conclusion: According to the findings of the study of expression changes in LncRNA TUG1 as a Tumor suppressor gene after treatment with thiosemicarbazones complexes Ni, both concentrations of the drug successfully increased LncRNA TUG1 expression. Overall, thiosemicarbazones complexes Ni had a positive effect on the LncRNA TUG1 increased mechanism over 72hour, and this increase in expressions was statistically significant (p-value 0.001). According to evidence, Ni -thiosemicarbazone complexes have a high anticancer potential and affirmative treatment of that.
Keywords: Ni -Thiosemicarbazones complexes, cDNA, LncRNA TUG1