Effects of hsa-piR-32877 Suppression with Antisense LNA GapmeRs on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia Cells

Sepideh Nasseri; Mohammadreza Sharifi; Valiollah Mehrzad

doi:10.22088/IJMCM.BUMS.12.1.18

Effects of hsa-piR-32877 Suppression with Antisense LNA GapmeRs on the Proliferation and Apoptosis of Human Acute Myeloid Leukemia Cells

Int J Mol Cell Med. 2023;12(1):18-29. doi: 10.22088/IJMCM.BUMS.12.1.18.

Authors

Sepideh Nasseri¹, Mohammadreza Sharifi¹, Valiollah Mehrzad²

Affiliations

¹ Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
² Department of Internal Medicine, Division of Hematology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Acute myeloid leukemia (AML) is an invasive form of hematologic malignancies which results in the overproduction of myeloid cells in the bone marrow. Aberrant expression of piwi-interacting RNAs (piRNAs) which belong to small non-coding RNAs, play important roles in different cancer cells' progress. hsa- piR- 32877 is up-regulated in AML. Down regulation of hsa-piR-32877 by antisense LNA GapmeRs could be potential for suppression of myeloid cell proliferation and induce myeloid cell apoptosis. We have blocked the expression of hsa-piR-32877 by antisense LNA GapmeRs in human bone marrow blast cells, and the M-07e cell line. Samples were transfected with antisense LNA GapmeRs at 24, 48, and 72 hours. The Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to investigate the expression of hsa-piR-32877, CASP3, and CASP9. Both CASP3 and CASP9 play important roles in apoptosis. Cell proliferation was studied via CFSE (carboxyfluorescein diacetate succinimidyl ester) assay. Results showed that hsa-piR-32877 was down-regulated by antisense LNA GapmeRs in the patient and cell line samples. Also, after transfection, cell proliferation and apoptosis decreased and increased, respectively. Our data suggested that hsa-piR-32877 suppression may act as a novel therapeutic method for the inhibition of human leukemic cells proliferation in AML.

Keywords: Acute myeloid leukemia; Antisense LNA GapmeRs; CASP3; CASP9; hsa-piR-32877.