RETRACTED: miRNA-193a-3p Regulates the AKT2 Pathway to Inhibit the Growth and Promote the Apoptosis of Glioma Cells by Targeting ALKBH5

Abstract

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.

Microarray data analysis to identify miRNA biomarkers and construct the lncRNA-miRNA-mRNA network in lung adenocarcinoma

“…Hsa-miR-3944 and hsa-miR-3652 may serve as new biomarkers in LUAD. [38][39][40] hsa-miR-15b-5p ↓ NB [41] hsa-miR-195-5p ↓ NSCLC, EC, CC [42][43][44] hsa-miR-193a-3p ↓ G, CC [45,46] hsa-miR-30a-3p ↓ NSCLC, GC, HCC [47][48][49] hsa-miR-145-5p ↓ HCC, GC [50,51] hsa-miR-451a ↓ NSCLC, CC, [52,53] hsa-miR-665 ↑ NSCLC, GC, BC [54][55][56] hsa-miR-144-3p ↓ NSCLC, GC, CC [57][58][59] hsa-miR-224-3p ↑ NSCLC [60] BC = breast cancer, CC = colorectal cancer, EC = esophageal cancer, G = glioma, GC = gastric cancer, HCC = hepatocellular carcinoma, NB = neuroblastoma, NSCLC = non-small cell lung cancer.…”

Role of m6A writers, erasers and readers in cancer

“…METTL3 regulates MGMT, ANPG, COL4A1, MALAT1, and UBXN1 expression in an m6A-dependent manner and promotes the progression of malignant glioma [303][304][305]307]. ALKBH5 regulates FOXM1, G6PD, SOX2, and AKT2 expression in an m6A-dependent manner to promote cancer cell proliferation, invasion and drug resistance [101,112,[309][310][311]. The YTHDF protein family regulates LXRA [312], HIVEP2 [312], MYC [313], VEGFA [313], and UBXN1 [305] expression in an m6A-dependent manner and promotes the occurrence, metastasis and drug resistance of malignant gliomas.…”

Epi‐miRNAs: Modern mediators of methylation status in human cancers

“…Focusing on m6A demethylases, recent studies have strongly demonstrated the tumor‐suppressive role of miR‐1266 and miR‐607 in CRC and NSCLC, respectively, through directly targeting and reducing FTO levels (Mo et al, 2021; Shen et al, 2018), while miR‐193a‐3p‐targeting of ALKBH5 impedes growth and enhance apoptosis of glioma cells through the AKT2 pathway both in vitro and in vivo (Cui et al, 2021). Besides m6A, knockdown of m1A demethylase ALKBH1 by miR‐339‐5p has been demonstrated to restrain GC cell proliferation and metastasis (Wang et al, 2020), highlighting a wider tumor‐suppressive role of epi‐miRs regulating RNA methylation machineries.…”

“…Glioma is the most frequent primary malignancy of the central nervous system, and GBM represents the most lethal disease subtype, with an average of 1‐year survival following diagnosis (Jones et al, 2021; Lapointe et al, 2018). With respect to disease prognosis, downregulation of miR‐133b, regulating EZH2, as well as of miR‐146b‐5p and miR‐193a‐3p expression, both targeting members of RNA methylation machinery, is associated with poor prognosis and survival outcome of the patients (Cui et al, 2021; J. Liu, Xu, et al, 2015; Xue et al, 2018).…”