Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients

Abstract

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers’ attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.

lncRNA GAS5 Induces Cell Apoptosis in Acute Myeloid Leukemia by Targeting Nrf2

“…AML is a heterogeneous malignant hematologic tumor. Chromosomal translocation is the commonest cause of the malignant transformation of hematopoietic progenitor cells [20]. AML patients suffer mainly * indicated that the comparison with NC group showed remarkable difference (P < 0:05).…”

“…AML is a heterogeneous malignant hematologic tumor. Chromosomal translocation is the commonest cause of the malignant transformation of hematopoietic progenitor cells [ 20 ]. AML patients suffer mainly from the blocking of normal differentiation and apoptosis of hematopoietic cells, the abnormal proliferation of bone marrow hematopoietic cells, and the accumulation of a large number of immature progenitor cells in the bone marrow peripheral blood.…”

Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia

“…This suggests that in AML GAS5 has a tumor-suppressive function and it was also found that lower expression of GAS5 was associated with inferior outcome among younger AML-NK patients [85]. As is the case with CLL, in AML GAS5 exerts its tumor-suppressor function, acting as a decoy for miR-222 [85].…”

“…There are only few studies examining GAS5 in AML, one of them examining GAS5 gene polymorphisms and their impact on AML prognosis [84]., Only two studies were investigating expression level of GAS5 in AML samples and based on their findings GAS5 expression level in AML patients was lower compared to healthy controls [82,85]. This suggests that in AML GAS5 has a tumor-suppressive function and it was also found that lower expression of GAS5 was associated with inferior outcome among younger AML-NK patients [85]. As is the case with CLL, in AML GAS5 exerts its tumor-suppressor function, acting as a decoy for miR-222 [85].…”

Recent Advances towards the Understanding of Secondary Acute Myeloid Leukemia Progression

“…Additionally, the lncRNA growth arrest-specific transcript 5 (GAS5) acts as both a negative regulator of the oncogenic miR-222 and a positive regulator of the tumor suppressor PTEN. Pavlovic et al observed lower levels of GAS5 in sAML compared with healthy donors [ 127 ].…”