CircRNA circ_POLA2 is Upregulated in Acute Myeloid Leukemia (AML) and Promotes Cell Proliferation by Suppressing the Production of Mature miR-34a

Li, Hong; Bi, Kehong; Feng, Saran; Wang, Yan; Zhu, Chuansheng

doi:10.2147/cmar.s281690

Cited by 17 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aberrant expression of circRNAs plays a crucial role in the development of many cancers (25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

Yang

Han

et al. 2022

Preprint

View full text Add to dashboard Cite

Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML), but its regulatory mechanism remains unclear. Herein, we identify a novel m6A modification-related circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We find that the expression of Circ_0001187 is regulated by the modification of DNA methylation and histone acetylation, and its biogenesis is meditated by splicing factor EIF4A3. Knockdown of Circ_0001187 significantly promotes the proliferation and inhibits the apoptosis of AML cells in vitro and in vivo, while overexpression of Circ_0001187 exerts the opposite effects. Moreover, we prove that Circ_0001187 enhances METTL3 protein degradation, which further decreases mRNA m6A modification in AML cells. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression RNF113A. And RNF113A functions as an E3 ubiquitin ligase to mediate METTL3 ubiquitin/proteasome-dependent degradation by K48-linked polyubiquitin chains. Collectively, our findings highlight the potential clinical implications of Circ_0001187 as a key tumor suppressor of AML via the miR-499a-5p/RNF113A/METTL3 pathway.

show abstract

“…Aberrant expression of circRNAs plays a crucial role in the development of many cancers (25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

Yang

Han

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The knockdown of circ_0058058 can suppress the progression of AML by modulating the sequestration of miR‐4319 and thereby regulating the expression of EIF5A2 23 . AML samples exhibit the upregulation of circ_POLA2, which can inhibit mature miR‐34a production and thereby promote cellular proliferation 24 25 .…”

Section: Discussionmentioning

confidence: 99%

“… 23 AML samples exhibit the upregulation of circ_POLA2, which can inhibit mature miR‐34a production and thereby promote cellular proliferation. 24 Moreover, circRNAs can offer value as diagnostic biomarkers in this oncogenic context, as in the case of circ_0002232, which offers value as a biomarker of AML that has been posited to function through a circ_0002232/miR‐92a‐3p/PTEN ceRNA regulatory pathway. 25 Other circRNA profiling and bioinformatics studies have also identified hsa_circ_0004277 as a promising AML‐related biomarker, 26 and the annexin A2 circRNA has also been highlighted as a promising biomarker and therapeutic in this cancer.…”

Section: Discussionmentioning

confidence: 99%

Serum hsa_circ_0079480 is a novel prognostic marker for acute myeloid leukemia

Guo

Kou

Song

et al. 2022

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background The dysregulated expression of serum circular RNAs (circRNAs) has previously been linked to the prognosis of acute myeloid leukemia (AML) patients, but the clinical and prognostic relevance of serum hsa_circ_0079480 levels in this oncogenic setting have yet to be established. Herein, we assessed the putative prognostic relevance of circulating hsa_circ_0079480 levels in AML patient serum. Methods Serum was prepared from blood samples collected from 236 AML patients and 160 healthy controls, with hsa_circ_0079480 levels therein being quantified by quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) after which the clinical value of these levels was assessed. Results Acute myeloid leukemia patients were found to exhibit significant hsa_circ_0079480 upregulation in their serum as compared to serum from healthy controls, with such upregulation being most profound in individuals with M4/M5 type disease and to be more common in patients with poor cytogenic risk or high white blood cell counts. Receiver operating characteristic (ROC) curves demonstrated that serum hsa_circ_0079480 levels were able to effectively differentiate between patients with AML and healthy controls. Moreover, the upregulation of serum hsa_circ_0079480 was found to be closely related to clinicopathological findings and to be an independent predictor of reduced overall and relapse‐free survival among individuals diagnosed with AML. Furthermore, serum hsa_circ_0079480 levels were markedly decreased after treatment in this patient population, with these levels being lower in patients that achieved complete remission as compared to those patients that did not. Conclusion Levels of hsa_circ_0079480 in patient serum may offer value as a prognostic biomarker in AML.

show abstract

“…Cir_POLA2 has been reported as an oncogene of lung cancer [19]. It has been found that overexpression of Cir_POLA2 can promote the proliferation of acute myeloid leukemia (AML) cells [20].…”

Section: Discussionmentioning

confidence: 99%

Research on predicting the occurrence of hepatocellular carcinoma based on Notch signal-related genes using machine learning algorithms

Zhou

Cao

Xie

2022

Preprint

View full text Add to dashboard Cite

Background:Hepatocellular carcinoma (HCC) is a highly malignant malignant tumor, and is difficult to diagnose, treat and predict the prognosis. Notch signaling pathway can affect HCC. Therefore, our paper aimed to explore the prediction of the occurrence of hepatocellular carcinoma based on Notch signal-related genes using machine learning algorithms.Methods:In our presented study, we downloaded HCC data from TCGA and GEO databases. Firstly, we used machine learning methods to screen the hub Notch signal-related genes. Then, machine learning classification was used to construct a prediction model for the classification and diagnosis of HCC cancer. In our presented study, we also used bioinformatics methods to explore the relationship between the expression of these hub genes in the HCC tumor immune microenvironment to further improve the reliablity of the model.Results:After screening, we identified four hub genes of LAMA4, POLA2, RAD51 and TYMS, which were used as the final variables to construct the model. It was found that AdaBoostClassifie was the best algorithm for the classification and diagnosis model of HCC. The area under curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score of this model in the training set were 0.976, 0.881, 0.877, 0.977, 0.996, 0.500 and 0.932; respectively. The AUC, accuracy, sensitivity, specificity, PPV, NPV and F1 score in the testing set were 0.934, 0.863, 0.881, 0.886, 0.981, 0.489 and 0.926. The AUC in the external validation set was 0.934. In the immune microenvironment, immune cell infiltration played an important role in HCC and was related to the expression of 4 hub genes. Further researches found that patients in the low-risk group of HCC were more likely to have immune escape.Conclusion: Notch signaling pathway were closely related to the occurrence and development of HCC. The HCC classification and diagnosis model established based on this had a high degree of reliability and stability.

show abstract

CircRNA circ_POLA2 is Upregulated in Acute Myeloid Leukemia (AML) and Promotes Cell Proliferation by Suppressing the Production of Mature miR-34a

Cited by 17 publications

References 20 publications

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway

Serum hsa_circ_0079480 is a novel prognostic marker for acute myeloid leukemia

Research on predicting the occurrence of hepatocellular carcinoma based on Notch signal-related genes using machine learning algorithms

Contact Info

Product

Resources

About