Investigating the Effect of Thiosemicarbazones complexes Cu on Expression Changes of LncRNA TUG1 in Acute Lymphoblastic Leukemia
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Neda Zahmatkesh,1 Mahnaz Eskandari,2,* Golnaz 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
3. Assistant professor of Molecular Genetics, 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: Acute lymphoblastic leukemia (ALL) is a kind of leukemia that affects lymphoid progenitor cells in the bone marrow, blood, and extramedullary locations. While 80 percent of ALL cases occur in children, it is a life-threatening condition in adults. ALL has a bimodal incidence pattern, with the first peak occurring in childhood and the second peak happening around the age of 50. While dose-intensification techniques have improved results for pediatric patients, the prognosis for the elderly is still quite bad. Despite a high percentage of induction chemotherapy response, approximately 30–40% of adult ALL patients will achieve long-term remission. TUG1 appears to play a role in tumor growth and cell metabolism through regulating cell proliferation, invasion, metastasis, apoptosis, differentiation, and treatment resistance, according to several studies. Thiosemicarbazones are effective against a variety of tumors, including leukemia, pancreatic cancer, breast cancer, non-small cell lung cancer, cervical cancer, prostate cancer, and bladder cancer. The goal of this study was to see how the Cu-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 Cu were prepared according to the IC50 of the drug that consists of 15 and 16 µM. The Jurkat E6.1 cell line was treated by Cu at 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 Cu at 15 and 16µM concentrations, the expression of LncRNA TUG1decreased significantly as compared to the control group. According to the findings, doses of 15 and 16µM of Cu 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 Cu, both concentrations of the drug successfully increased LncRNA TUG1 expression. Overall, thiosemicarbazones complexes Cu 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, Cu-thiosemicarbazone complexes have a high anticancer potential and affirmative treatment of that.
- Keywords: Thiosemicarbazones complexes Cu, cDNA, GAPDH, LncRNA TUG1
