Long noncoding RNA PVT1: potential oncogene in the development of acute lymphoblastic leukemia

Authors: NARJES YAZDI, MOHAMMAD HOUSHMAND, AMIR ATASHI, ALIREZA KAZEMI, ALI ANJAM NAJMEDINI, MAHIN NIKOUGOFTAR ZARIF

Abstract: Emerging evidence shows that long noncoding RNAs (lncRNAs) participate in various cellular processes, and that plasmacytoma variant translocation 1 (PVT1), a newly described oncogene that interacts with various molecules such as p15, p16, NOP2, and c-Myc, is a major contributing factor in tumor development. However, the role of this oncogene remains unknown in the pathogenesis of acute lymphoblastic leukemia (ALL), the most prevalent form of childhood leukemia. In this study, we first measure the expression level of PVT1 in a Jurkat cell line, then small interfering (siRNA) PVT1 is applied to demonstrate the impact of PVT1 knockdown in apoptosis, proliferation, the cell cycle, and its downstream targets. Our findings show that lncRNA was significantly higher in the ALL cell line than normal lymphocytes and that PVT1 knock-down increased the rate of apoptosis, caused G0/G1 arrest in the cell cycle, reduced the proliferation rate, and, above all, reduced the stability of c-Myc protein. All findings were confirmed at the molecular level. Our results may indicate the role of PVT1 knock-down in the suppression of ALL development and might provide an option for targeted therapy for leukemic conditions.

Keywords: Long noncoding RNA, PVT1, acute lymphoblastic leukemia, c-Myc, siRNA

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