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

Abstract

Objective. This study is aimed at investigating the molecular mechanism of lncRNA GAS5-induced cell apoptosis in acute myeloid leukemia (AML) by targeting Nrf2. Methods. The RNA interfering technique was utilized to silence THP-1 in AML cell line, and lncRNA GAS5 expression in cell line was determined by real-time PCR. EdU experiment and flow cytometry were used to detect the apoptosis and proliferation ability of cells in different groups. PD-L1, STAT3, AKT, and MMP9 expressions were determined by Western blot. Results. The si-RNA significantly inhibited the expression of lncRNA GAS5 in THP-1 cells. Compared with the si-NC group, the difference in cell apoptosis between lncRNA GAS5 and Nrf2 groups was significant ( P < 0.05 ). Compared with the lncRNA GAS5 group, the number of apoptotic cells in the lncRNA GAS5+Nrf2 group significantly reduced ( P < 0.05 ). Compared with the si-NC group, the differences in the levels of four proteins between lncRNA GAS5 and Nrf2 groups were significant ( P < 0.05 ). In lncRNA GAS5+Nrf2 and lncRNA GAS5 groups, PD-L1 expression increased, while the expression of STAT3, AKT, and MMP9 decreased. Conclusion. In AML cells, lncRNA GAS5 with Nrf2 could regulate the proliferation and apoptosis of AML cells. lncRNA GAS5 inhibited Nrf2 expression, regulated cell apoptosis and proliferation, and further inhibited the progression of AML disease.

Long non-coding RNAs: emerging functional players in the pathobiology and progression of myeloid leukemia

“…The lncRNA SNHG5 was found to be upregulated by YY1 in AML; downstream, SNHG5 was shown to regulate AML angiogenesis by activating the connective tissue growth factor (CTGF)/vascular endothelial growth factor A (VEGFA) by directly targeting miR-26b . Another lncRNA that regulates angiogenesis in AML is H22954, which was found to target the 3' untranslated region (UTR) of PDGFRA and reduce its half-life, thus inhibiting angiogenesis in AML (Li X. et al, 2022). Another interesting mechanism by which lncRNAs regulate gene expression is at the translational level, such as in the antisense lncRNA PU.1-AS that originates from an intronic promoter in PU.1.…”

“…Frontiers in RNA Research frontiersin.org and CML patients have been suggested as prognostic markers for early diagnosis (Table 3) (Wang et al, 2014;Wang X. et al, 2018;Díaz-Beyá et al, 2015;Hao and Shao, 2015;Wu et al, 2015;Fernando et al, 2017;Yao et al, 2017;Ma et al, 2020Ma et al, , 2018Zhang T. et al, 2018;Zhang W. et al, 2020;Zhang X. et al, 2020;Zhang F. et al, 2020;Izadifard et al, 2018;Jia et al, 2018;Pashaiefar et al, 2018;Qin et al, 2018Qin et al, , 2022Yang et al, 2018;Papaioannou et al, 2019b;Cai et al, 2019;Chen et al, 2019;El-Khazragy et al, 2019;Huang et al, 2019;Lei et al, 2019;Li et al, 2019;Sellers et al, 2019;Zhang and Tao, 2019;Feng et al, 2020b;Chen et al, 2020;Ketab et al, 2020;Peng et al, 2020;Qu et al, 2020;Tan et al, 2020;Xu et al, 2020;Gao, 2021a;Saad et al, 2021;Gamaleldin et al, 2021;Masoud Eslami et al, 2021;Pavlovic et al, 2021;…”

“…Resistance to chemotherapy with subsequent relapse was also observed in patients with low IRAIN expressions (Pashaiefar Hussein et al, 2023). Recently, lower GAS5 expressions during diagnosis have been related to adverse prognosis in AML patients (Ketab et al, 2020;Pavlovic et al, 2021;Qin et al, 2022). Separate studies have associated the expression pattern of GAS5 with the expression profiles of its targets, miRNA-222 and NR3C1, as dual biomarkers for prognosis in young and adult AML patients, respectively (Ketab et al, 2020;Pavlovic et al, 2021).…”

Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

“…Leukemia is a malignant tumor of the hematopoietic system ( 148 ). It is known that cell cycle is closely related to proliferation ( 149 ), among which cdc2/cyclin B is a complex that controls G2/M cell cycle transition ( 150 ). PBK/TOPK is a substrate of cdc2/cyclin B that can promote mitosis ( 151 ), and PBK/TOPK protein is upregulated in a variety of hematological malignancies, which is important for the proliferation and malignant transformation of hematological tumors ( 152 ).…”

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

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”