LINC00987 knockdown inhibits the progression of acute myeloid leukemia by suppressing IGF2BP2-mediated PA2G4 expression

Abstract

This study aimed to investigate the role and potential mechanisms of LINC00987 in acute myeloid leukemia (AML) progression. The expression of LINC00987 in bone marrow specimens of AML patients and cell lines was measured by quantitative reverse transcription PCR (RT-qPCR). Small interfering RNA targeting LINC00987 (si-LINC00987) was transfected into AML cell lines HL-60 and KG-1, and the proliferation, invasion and apoptosis were detected with Cell Counting Kit-8 (CCK-8), Transwell and flow cytometry, respectively. Moreover, the binding between LINC00987 and insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was validated with an RNA pull-down assay. Co-immunoprecipitation assay was used to verify the binding between IGF2BP2 and proliferationassociated 2G4 (PA2G4). Then rescue experiments were performed to explore the effects of LINC00987/IGF2BP2/ PA2G4 axis on HL-60 and KG-1 cell functions. Additionally, HL-60 cells transfected with si-LINC00987 were injected into mice, followed by the evaluation of xenograft tumor growth. LINC00987 was upregulated in AML patient specimens and cell lines. LINC00987 knockdown inhibited proliferation and invasion and promoted apoptosis in AML cells. LINC00987 could bind with IGF2BP2 and promote its expression, and IGF2BP2 overexpression reversed the effects of LINC00987 knockdown on the proliferation, invasion and apoptosis in AML cells. Besides, IGF2BP2 could bind with PA2G4. IGF2BP2 knockdown inhibited proliferation and invasion, and promoted apoptosis in AML cells, whereas PA2G4 overexpression reversed these effects. Additionally, the LINC00987 knockdown inhibited the xenograft tumor growth of AML in vivo. Knockdown of LINC00987 inhibits AML cell proliferation and invasion, and promotes apoptosis in vitro and reduces tumor growth in vivo by suppressing IGF2BP2-mediated PA2G4 expression. Anti-Cancer Drugs 33: e207-e217

An Immunogenic Cell Death-Based Risk model Predicts Prognosis and Indicates Immune Infiltration Landscape in Acute Myeloid Leukemia

“…LncRNA plays an important role in occurrence, development, and prognosis of AML [22]. Among seven lncRNAs in the prognostic risk model, the lncRNA LINC00987 and MIR133A1HG deregulation were demonstrated signi cantly correlated with prognosis and tumor progression in AML [23,24], indicated that LINC00987 and MIR133A1HG may serve as new promising individualized therapeutic targets for the treatment of AML [25]. Our data rea rmed its potential value as therapeutic targets in AML.…”

LINC00173 facilitates tumor progression by stimulating RAB1B‐mediated PA2G4 and SDF4 secretion in nasopharyngeal carcinoma

“…It can bind YTHDF2 to increase FYN expression and promote hepatocellular carcinoma metastasis [ 42 ]. Moreover, PA2G4 is reported to be regulated by noncoding RNA [ 43 , 44 ]. For example, circERBB2 promotes gallbladder cancer progression by regulating PA2G4‐modulated ribosomal DNA transcription [ 43 ].…”

“…For example, circERBB2 promotes gallbladder cancer progression by regulating PA2G4‐modulated ribosomal DNA transcription [ 43 ]. Knockdown of LINC00987 suppresses acute myeloid leukemia progression by inhibiting the IGF2BP2‐mediated PA2G4 expression [ 44 ]. More importantly, the expression of PA2G4 has been reported to be elevated in NPC and is associated with a poor prognosis [ 45 ].…”

Systematic optimization of siRNA productive uptake into resting and activated T cellsex vivo

“…siRNAs, a novel precision medicine drug class, hold promise to meet this clinical need to selectively inhibit any sequence (including noncoding sequences[6]) in the transcriptome. However, siRNA delivery to immune cells (i.e.…”