miR‐345‐5p regulates proliferation, cell cycle, and apoptosis of acute myeloid leukemia cells by targeting AKT2

Abstract

Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease, which is caused by hematopoietic stem cell abnormalities. Epigenetic regulation, especially of microRNAs (miRNAs), mostly results from external or environmental effects and is critical to AML. In this study, for the first time, we report that decreased expression of miR‐345‐5p facilitates the proliferation of leukemia cells in AML. Further study demonstrated that AKT1/2 was the target of miR‐345‐5p and was responsible for the dysregulation of leukemia cell proliferation and apoptosis. Inhibition of AKT1/2 ameliorated this malignant effect, which provides new insight into AML diagnosis, treatment, prognosis, and next‐step translational investigations.

Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis through miR-497-5p/AKT3 axis

“…It has been reported that the AKT signaling pathway is crucial for proliferation in leukemia cells, suggesting that AKT may be a new avenue for leukemia treatment [36,37]. Recently, a study report that AKT1/2 was overexpressed in K562 cells and promoted cell proliferation and protected the cells from apoptosis [38]. In the present study, our results suggested that AKT signaling pathway was activated in vitro and vivo.…”

Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

“…An oncogenic activity of lncRNA was also shown by HOTAIR that regulating the expression of c-Kit in AML cells through competitively binding miR-193a, an important tumor-suppressor miRNA to predict a poor clinical outcome [190]. HOTAIRM1, a lncRNA located in the HOXA genomic region, is related to myeloid differentiation which sequestered miR-20a, miR-106b and ↑in AML cell lines and CN-AML with biallelic CEBPA p27kip1 Role in promoting cells proliferation is to sequester hnRNP I to inhibit the expression of the cell cycle regulator p27kip1 [167] ↑in HL-60 and HL-60/ADR miR-125a Poor chemotherapy overcome [189] HOTAIR ↑in de novo AML patients miR-193a;c-Kit Increase AML cells proliferation, inhibited apoptosis and infiltration of leukemic blasts and number of AML cells colony formation, and shorten overall survival time [190] ↑in LSC p15 Promote the self-renewal of leukemia stem cells [191] CCAT1 ↑in HL60 and AML PB miR-155, c-Myc Upregulated c-Myc expression to increased cells proliferation and differentiation by its competing endogenous RNA (ceRNA) activity on miR-155 [192] FTX ↑in U937 and THP-1 miR-342, ALG3 Drug resistance [193] PANDAR ↑ANDARLINK Predict adverse prognosis in AML [181] HOXA-AS2 ↑in APL TRAIL-mediated pathway Lead to fine-tuning of apoptosis during ATRA-induced myeloid differentiation [194] ↑00PERLINK \l "_ENREF_200" \o "Zhao H, 2013 #197" or><adriamycin-based chemotherapy and in U/A and T/A cells miR-520c-3p/ S100A4 Axis Knockdown of lncRNA HOXA-AS2 inhibited ADR cell proliferation and chemoresistance of AML by the miR-520c-3p/ S100A4 Axis, and promoted apoptosis [195] HOTAIRM1 is an oncogenic lncRNA that upregulated c-Myc via its ceRNA activity on miR-155 to repress monocytic differentiation and promote cell growth [192]. The host non-coding transcript of miR-223 of linc-223, found downregulated in AML, is a functional lncRNA which regulated proliferation and differentiation of AML cells by binding miR-125-5p [203].…”

“…Knocking down HOTAIRM1 would prohibit all-trans retinoic acid (ATRA)-induced granulocyte differentiation [161]. The fact that HOTAIRM1 came from the HOXA cluster might imply that it could ↓in various subtypes of AML E2F1 Lead to AML cell apoptosis [134] ↓in AML with adverse prognosis Impair differentiation [135] ↓in various subtypes of AML FBXW7 Increase cell proliferation and enhance apoptosis [136] miR-339-5p ↓in AML cells SOX4 Inhibit cell proliferation of AML cells [137] miR-345-5p Mutated NPM1 ↓in AML cell lines AKT1/2 Facilitate the proliferation of leukemia cells [138] miR-370 ↓iR-370 NF1 Activation of the RAS signaling pathway [139] miR Let-7c ↓in AML patients with t(8;21) and inv (16) PBX2 Promotes granulocytic differentiation [140] Abbreviations: HSPC hematopoietic stem and progenitor cell, LSC leukemia stem cells, MSCs bone marrow mesenchymal stromal cells, NSG NOD/SCID/IL-2rγnull, allo-HSCT allogeneic hematopoietic stem cell transplantation, PB peripheral blood, BM bone marrow regulate nearby genes in the HOXA cluster, although this warranted further investigation. The other lncRNA, NEAT1, was significantly downregulated by PML-RARα in de novo APL samples compared with those of healthy donors.…”

miR‑345‑3p serves a protective role during gestational diabetes mellitus by targeting BAK1

“…miRNAs are a class of highly evolutionarily conserved, single-chain, small-molecule, non-coding RNAs, measuring 18-23 nucleotides in length, that serve a regulatory role at the epigenetic level (11). Previous studies investigating miR-345 have focused on cancer, including prostate (12,13) and colorectal cancer (14), as well as acute lymphocytic leukemia (15). Studies have identified miR-345 as a key regulator in a variety of types of cancer, primarily via its target genes and signaling pathways (12)(13)(14)(15)(16).…”

“…Previous studies investigating miR-345 have focused on cancer, including prostate (12,13) and colorectal cancer (14), as well as acute lymphocytic leukemia (15). Studies have identified miR-345 as a key regulator in a variety of types of cancer, primarily via its target genes and signaling pathways (12)(13)(14)(15)(16). miR-345 can also act as a tumor suppressor to affect cell epigenetic regulation, proliferation, apoptosis, differentiation, metabolism and chemosensitivity (17)(18)(19).…”