Evaluating the effects of chemotherapy drugs and thiosemicarbazone complexes on the alteration of SNHG16 expression in Acute Lymphoblastic Leukemia

Fatemeh Erfanipour; Fatemeh Ghorbani; Sina Mirzaahmadi; Golnaz Asaadi Tehrani

doi:10.18502/ijpho.v13i3.13130

Fatemeh Erfanipour Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Fatemeh Ghorbani Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Sina Mirzaahmadi Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Golnaz Asaadi Tehrani Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran

DOI: https://doi.org/10.18502/ijpho.v13i3.13130

Keywords: Acute lymphoblastic leukemia, Chemotherapy, Drugs, Long noncoding RNA

Abstract

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease that afflicts both children and adults. It starts from the bone marrow (soft and spongy tissue inside the bone) where immature white blood cells or lymphocytes are formed. This study aims to compare chemotherapy drugs, methotrexate (MTX), cyclophosphamide, cytarabine (Ara-C) and mercaptopurine (6mp) with nickel (Ni) and copper (Cu) complexes of thiosemicarbazone (TSCZ) in terms of their effects on the changes of Small Nucleolar RNA Host Gene 16(SNHG16) long non coding RNA (lncRNA) expression in the ALL cell line.

Materials and Methods: this experimental study was conducted on various concentrations of chemotherapy drugs including MTX, CP, Ara-C, 6mp and Ni and Cu complexes of TSCZ. The Jurkat E6.1 cell lines were subjected to passage in different groups and times (24, 48, and 72h) and then treated with the chemotherapy drugs. After RNA extraction and cDNA synthesis, the SNHG16 gene expression was evaluated by Real-Time PCR, and the results were analyzed by the Rest software.

Results: As the results indicated, within 24h, MTX (0.77, 0.72), CP (0.61, 0.7), ara-C (0.78, 0.87), Cu (0.91, 0.95) and Ni (0.94, 0.79) complexes as well as complex 1(0.73) and 2 (0.94) decreased the expression of SNHG16 gene significantly (P<0.001). Furthermore within 48h, under the influence of CP (0.86, 0.89) and Ara-C (0.94, 0.97) as well as Cu (0.96) and Ni (0.98) complexes, the gene expression continued to decline(P<0.001).The greatest effect of chemotherapy drugs belonged to the combination of 1μM of ara-C and 5μM of 6mp.(P<0.001).

Conclusion: It was found that gene expression analysis is a feasible method to identify the pathways affected by the standard induction chemotherapy in ALL patients. This finding promotes the development of novel targeted drugs and biomarkers to categorize disease aggressiveness and evaluate treatment responses.