Downregulation of circ_0012152 inhibits proliferation and induces apoptosis in acute myeloid leukemia cells through the miR‐625‐5p/SOX12 axis

Guo

Oxidative Medicine and Cellular Longevity

et al. 2022

Background. It is well known that microRNAs (miRNAs) interfere with the progression of various human malignancies. This article is aimed at exploring the regulating role of miR-342-3p in acute myeloid leukemia (AML) and its mechanism. Methods. We used the Gene Expression Omnibus (GEO) database to determine miR-342-3p differential expression patterns in AML patients’ plasma and cells as well as healthy individuals’ plasma and T cells. Quantitative real-time PCR and Western blotting were performed for plasma and cell miR-342-3p and SRY-related high-mobility-group box (SOX12) expression quantification, and cell counting kit-8 assay and flow cytometry were used for the determination of AML cell growth, cycle, and apoptosis. A dual-luciferase reporter gene assay was further carried out to identify the targeted association between miR-342-3p and SOX12 mRNA 3 ′ UTR after prediction by a bioinformatics website. Pearson’s correlation analysis was performed to analyze the connection between miR-342-3p and SOX12 expressions. The LinkedOmics database was utilized to explore the downstream pathways in which SOX12 was enriched. Results. Evidently downregulated plasma miR-342-3p and markedly elevated SOX12 were observed in AML patients versus healthy individuals. miR-342-3p mimics suppressed AML cell growth, enhanced apoptosis, and induced G0/G1 phase arrest; conversely, enhanced capacity of AML cells to proliferate, suppressed apoptosis, and accelerated cell cycle were observed after treatment with miR-342-3p inhibitors. SOX12 was confirmed as miR-342-3p’s target gene. Overexpressing or knocking down SOX12 reversed miR-342-3p’s impacts on AML cell growth, apoptosis, and cycle. Upregulated SOX12 was positively related to DNA replication and RNA polymerase signaling pathways. Conclusion. miR-342-3p affects apoptosis of AML cells and their ability to proliferate via targeted regulation of SOX12.

Section: Discussionmentioning

confidence: 99%

miR-342-3p Inhibits Acute Myeloid Leukemia Progression by Targeting SOX12

Guo

Oxidative Medicine and Cellular Longevity

et al. 2022

“…In malignant pleural mesothelioma (MPM) (34,35) and thyroid cancer (TC) (36,37), miR-625 was found to be upregulated. It is downregulated in bladder cancer (38), nasopharyngeal carcinoma (NPC) (39), lung cancer (40)(41)(42)(43)(44)(45)(46), HCC (47), cervical cancer (CC) (48,49), osteosarcoma (50), melanoma (51)(52)(53)(54), laryngeal squamous cell carcinoma (LSCC) (55), acute myeloid leukemia (AML) (56), BC (57)(58)(59), glioma (60,61), esophageal cancer (EC) (62)(63)(64), clear cell renal cell carcinoma (65), GC (66)(67)(68)(69)(70), and pancreatic ductal adenocarcinoma (PDAC) (71). In colorectal cancer (CRC), the expression of miR-625 seems to vary, being either high or low.…”

Section: Mir-625 In Cancers Aberrant Expression Of Mir-625 In Cancersmentioning

confidence: 99%

“…Gain-of-function assays suggested that after transfection with miR-625-5p, the proliferation of U937 and HL60 cells was significantly reduced, whereas the miR-625-5p + SOX12 group had the opposite pattern. Therefore, miR-625-5p can regulate AML cell growth by targeting SOX12 (56). Ma et al also pointed out that miR-625 participated in the occurrence and development of AML through Wnt/β-catenin signaling (110).…”

Section: Acute Myeloid Leukemia (Aml)mentioning

confidence: 99%

“…Further research revealed that circ0016418 exerted a carcinogenic effect by regulating the miR-625/YY1 axis. Shang et al found that down-regulation of circ0012152 suppressed proliferation and induced apoptosis of AML cells via the miR-625-5p/SOX12 axis (56). In addition, the circMMP11/miR-625-5p/ZEB2 axis is involved in the BC cell proliferation, migration and apoptosis (57).…”

Section: Circrnas and Mir-625mentioning

confidence: 99%

See 1 more Smart Citation

Crucial Roles of miR-625 in Human Cancer

et al. 2022

Genetic and epigenetic characteristics are core factors of cancer. MicroRNAs (miRNAs) are small non-coding RNAs which regulate gene expression at the post-transcriptional level via binding to corresponding mRNAs. Recently, increasing evidence has proven that miRNAs regulate the occurrence and development of human cancer. Here, we mainly review the abnormal expression of miR-625 in a variety of cancers. In summarizing the role and potential molecular mechanisms of miR-625 in various tumors in detail, we reveal that miR-625 is involved in a variety of biological processes, such as cell proliferation, invasion, migration, apoptosis, cell cycle regulation, and drug resistance. In addition, we discuss the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks and briefly explain the specific mechanisms of competing endogenous RNAs. In conclusion, we reveal the potential value of miR-625 in cancer diagnosis, treatment, and prognosis and hope to provide new ideas for the clinical application of miR-625.

“…Knockdown of circ_0002483 inhibited AML cell proliferation and facilitated cell cycle arrest and apoptosis by regulating miR-758-3p/MYC axis ( Xiao et al, 2021 ) ( Figure 4A ). Shang et al found that the expression of circ_0012152 was enhanced in AML tissues and cells, circ_0012152 knockdown inhibited cell proliferation, induced cell apoptosis and facilitated death in AML cells by regulating miR-625-5p/SOX12 axis ( Shang et al, 2021 ) ( Figure 4A ). In addition, Lux et al reported that circBCL11B exclusively expressed in AML patients but not detected in healthy hematopoietic stem and progenitor cell samples, inhibition of circBCL11B suppressed leukemic cell proliferation and led to enhanced cell death of leukemic cells ( Lux et al, 2021 ).…”

Section: Circrnas Regulte Cell Differentiation Cell Cycle Progression...mentioning

confidence: 99%

Functions and clinical significance of circular RNAs in acute myeloid leukemia

et al. 2022

Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNA molecules. Four types of circRNAs have been reported in animal cells, and they have typical characteristics in their biogenesis, nuclear export and degradation. Advances in our understanding of the molecular functions of circRNAs in sponging microRNAs, modulating transcription, regulating RNA-binding proteins, as well as encoding proteins have been made very recently. Dysregulated circRNAs are associated with human diseases such as acute myeloid leukemia (AML). In this review, we focus on the recently described mechanisms, role and clinical significance of circRNAs in AML. Although great progress of circRNAs in AML has been achieved, substantial efforts are still required to explore whether circRNAs exert their biological function by other mechanisms such as regulation of gene transcription or serving as translation template in AML. It is also urgent that researchers study the machineries regulating circRNAs fate, the downstream effectors of circRNAs modulatory networks, and the clinical application of circRNAs in AML.