BTYNB, an inhibitor of RNA binding protein IGF2BP1 reduces proliferation and induces differentiation of leukemic cancer cells

Alam Jamal; Mahmood Hassan Dalhat; Sadaf Jahan; Hani Choudhry; Mohammad Imran Khan

doi:10.1016/j.sjbs.2023.103569

BTYNB, an inhibitor of RNA binding protein IGF2BP1 reduces proliferation and induces differentiation of leukemic cancer cells

Saudi J Biol Sci. 2023 Mar;30(3):103569. doi: 10.1016/j.sjbs.2023.103569. Epub 2023 Jan 25.

Authors

Alam Jamal¹, Mahmood Hassan Dalhat¹, Sadaf Jahan², Hani Choudhry^{1

3}, Mohammad Imran Khan^{1

3}

Affiliations

¹ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah, Saudi Arabia.
³ Centre of Artificial Intelligence for Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Abstract

Leukemia is a group of diseases characterized by altered growth and differentiation of lymphoid or myeloid progenitors of blood. The existence of specific clusters of cells with stemness-like characteristics like differentiation, self-renewal, detoxification, and resistance to apoptosis in Leukemia makes them difficult to treat. It was recently reported that an oncofetal RNA binding protein, insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), maintains leukemic stem cell properties. BTYNB is an inhibitor of IGF2BP1 that was shown to affect the biological functions of IGF2BP1 however, the effect of BTYNB in Leukemia is not properly established. In this study, we assessed the effect of BTYNB on leukemic cell differentiation and proliferation. We performed cell viability assay to assess the effect of BTYNB in leukemic cells. We then assessed cell morphology of the leukemic cells treated with BTYNB. Further, we conducted an apoptosis assay and cell cycle assay. We found the cell viability of leukemic cells was significantly decreased post treatment with BTYNBs. Further, a noticeable morphological change was observed in BTYNB treated leukemic cells. BTYNB treated leukemic cells showed increased cell death and cell cycle arrest at S-phase. Evidence from the upregulation of BAK and p21 further confirmed apoptosis and cycle arrest. The gene expression of differentiation genes such as CD11B, ZFPM1, and KLF5 were significantly upregulated in BTYNB treated leukemic cells, therefore, confirming cell differentiation. Collectively, our study showed inhibition of IGF2BP1 function using BTYNB promotes differentiation in leukemic cells.

Keywords: BTYNB; Cell differentiation; IGF2BP1; Leukemia; RNA binding proteins.