LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia

Abstract

Correspondence: Man Huang (huangman770@163.com)As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2. regulate COL1A1 expression, thus enhancing proliferation and migration ability of breast cancer cells [7]. COL1A1-014 functions as a ceRNA in gastric cancer development via up-regulating CXCL12 and CXCR4 through interacting with miR-1273h-5p [8]. Up-regulation of lncRNA HOTAIR promotes PRAF2 expression via acting as a sponge of miR-326 in cutaneous squamous cell carcinoma [9]. LncRNA NEAT1 contributes to lung cancer cell proliferation and invasion via NEAT1/miR-1224/KLF3 ceRNA pattern [10].Long intergenic non-coding RNA 00221 (LINC00221) was reported to enhance the cisplatin resistance of non-small cell lung cancer [11]. Also, LINC00221 is a prognostic biomarker for patients with hepatocellular carcinoma [12]. Besides, GEPIA database (http://gepia.cancer-pku.cn/) indicated that LINC00221 was conspicuously down-regulated in acute myeloid leukemia. However, the expression pattern and functional role of LINC00221 in ALL are still uncovered. Thus, the study was designed to explore the function and underlying mechanism of LINC00221 in ALL cells. Materials and methods Cell cultureHuman ALL cell lines (Jurkat, CCRF-CEM, CEM/C1, 1301) and normal HEK 293T cell line were available from the ATCC (Manassas, VA) and cultivated in 5% CO 2 at 37 • C. Cell samples were all maintained in RPMI-1640 medium, with 10% FBS (HyClone, Logan, UT) and 1% penicillin-streptomycin as supplements. RNA...

LINC00265/miR-4500 Axis Accelerates Acute Lymphoblastic Leukemia Progression by Enhancing STAT3 Signals

“…29 LINC00221 regulates ATP2A2 expression by sponging miR-152-3p, exhibiting anti-proliferation and pro-apoptosis effects in ALL cells. 30 In the study, we found that miR-4500 inhibitors or overexpressed LINC00265 can up-regulate STAT3 expression, whereas miR-4500 mimics or STAT3 shRNAs eliminate the LINC00265-induced malignancy of ALL cells, specifically suppressing ALL cell proliferation and invasion. These results are consistent with the function of STAT3 in breast cancer 31 and head and neck cancer, 32 although they should be further examined in clinical samples.…”

“… 29 LINC00221 regulates ATP2A2 expression by sponging miR-152-3p, exhibiting anti-proliferation and pro-apoptosis effects in ALL cells. 30 …”

Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation, invasion, and migration of gastric cancer cells

“…ATP2A2, functioning as an ATP synthase-associated protein, plays a critical role in mitochondrial ion exchange and energy transmission, which significantly influences mitochondrial function[ 25 ]. Furthermore, ATP2A2 has been proven to be instrumental in regulating linc00221-mediated acute lymphoblastic leukemia cell proliferation and apoptosis[ 26 ]. Notably, overexpressed ATP2A2 has also been observed to promote the proliferation of colon cancer and prostate cancer cells[ 27 , 28 ].…”

Bioinformatics and Prediction Analysis of Long Non-coding RNAs in the Regulation of Glioblastoma Cell Migration and Invasion

“…Among them, LINC00221 promotes cisplatin resistance in non-small-cell lung cancer, leading to non-effective chemotherapy 28 . Additionally, LINC00221 suppresses the malignancy in acute lymphoblastic leukaemia (ALL) where its overexpression leads to an antiproliferative and pro-apoptotic effect in ALL cells 29 . Within the context of GBM, the literature regarding these four lncRNAs is very scarce.…”