LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR‐155

Yu, Yihua; Kou, Daqing; Liu, Bing; Huang, Yiran; Li, Shuangda; Qi, Yu; Guo, Yafei; Huang, Tong; Qi, Xia; Li, Jia

doi:10.1111/ijlh.13225

Cited by 41 publications

(42 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study show that LncRNA MEG3 regulates ALG9 by sponging miR-155 (26) and miR-155 regulates the pathogenesis of heart failure (27). These results are consistent with our experimental results.…”

Section: Discussionsupporting

confidence: 91%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: miR-155 is a widely reported carcinogenic miRNA, with up-regulated expression in a variety of human cancers. Methods: Liver cancer stem cells were isolated from Huh7 cells; gene infection, RT-PCR, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: we demonstrate that miR-155 inhibits the expression of MBD5 and METTL3 , reducing the expression of DNMT1. In particular, miR155 inhibits the interaction between MBD5 and DNMT1, thereby inhibiting the binding capacity among MBD5, DNMT1 and IGFII (H19 ICR, IGFII DMR, IGFII Enhancer) DNA, inhibiting IGFII DNA methylation modification. Importantly, miR-155 promotes the formation of DNA loops in the IGFII DNA region (H19 ICR-IGFII Enhancer, IGFII DMR-IGFII Enhancer). Therefore, miR155 promotes the binding ability of H19-pre miR675 to histone methyltransferases SUV39h2 dependent on the H19 ICR-IGFII enhancer DNA loop and enhances the methylation modification of histone H3 on the ninth lysine . Then, the binding ability of RNA polII to P300 was enhanced by the formation of H3K9me2-RNA polII-P300 complex. Furthermore, miR155 promotes the binding ability of the RNA PolII-P300 complex to the IGFII promoter dependent on the IGFII DMR-IGFII enhancer DNA loop and promotes the expression of IGFII. Further research shows that miR155 promotes the binding of IGFII to stemness factors and the loading of stemness factors into the promoter region of HGF, which promotes the expression of hepatocyte growth factor HGF. In particular, miR155 promotes the expression of albumin gene (ALB) via HGF-c-MET, and then promotes the Sirt1 expression through ALB. Strikingly, miR155 promotes the autophagy dependent on acetylase Sirt1,including that miR155 promotes LC3 activation dependent on acetylase sirt1 and enhances binding capacity of LC3 to TP53INP2 / DOR, ATG4, ATG3 and ATG7, and the binding ability of the interaction between ATG5, ATG12, ATG6L1, ATG9. More meaningfully, miR155 enhances the ability of H-Ras to bind to the autophagosomes Beclin1, vps34, vps5, Uvrage, bif1, Lamp1, Lamp2, Lamp3, Rubicon, Rab24 dependent on autophagy, thereby enhancing the expression of H-Ras. Furthermore, miR155 enhances the expression of pRaf1, pMEK1 / 2, pERK1 / 2, pElK, pJak, Jun, pAKT, pmTOR, P70S6K, 4E-BP1, SGK1, C-myc dependent on H-Ras.Finally, miR-155 promotes the malignant growth of human liver cancer stem cells mediated by H-Ras.Conclusions: these results provide a valuable theoretical basis for therapeutic targets of liver cancer based on miR-155.

show abstract

Section: Discussionsupporting

confidence: 91%

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

Lu¹,

Chen²,

Xin³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Taken together, although current literature shows no evidence for “MEG3” functions in GD, DES-Tcell suggests a potential association of this lncRNA to GD. This idea is strengthened by the Yu et al study that shows ‘miR-155’ (that we know to be involved in GD) is a direct target of the ‘MEG3’ which acts by sponging ‘miR-155’ in acute myeloid leukemia (AML) cells 113 . Therefore, this DES-Tcell association is suggested as potentially new immunological knowledge and should be considered a potential therapeutic target.…”

Section: Knowledgebase Utilities and Case Studiesmentioning

confidence: 99%

DES-Tcell is a knowledgebase for exploring immunology-related literature

Alsaieedi

Salhi

Tifratene

et al. 2021

Sci Rep

View full text Add to dashboard Cite

T-cells are a subtype of white blood cells circulating throughout the body, searching for infected and abnormal cells. They have multifaceted functions that include scanning for and directly killing cells infected with intracellular pathogens, eradicating abnormal cells, orchestrating immune response by activating and helping other immune cells, memorizing encountered pathogens, and providing long-lasting protection upon recurrent infections. However, T-cells are also involved in immune responses that result in organ transplant rejection, autoimmune diseases, and some allergic diseases. To support T-cell research, we developed the DES-Tcell knowledgebase (KB). This KB incorporates text- and data-mined information that can expedite retrieval and exploration of T-cell relevant information from the large volume of published T-cell-related research. This KB enables exploration of data through concepts from 15 topic-specific dictionaries, including immunology-related genes, mutations, pathogens, and pathways. We developed three case studies using DES-Tcell, one of which validates effective retrieval of known associations by DES-Tcell. The second and third case studies focuses on concepts that are common to Grave’s disease (GD) and Hashimoto’s thyroiditis (HT). Several reports have shown that up to 20% of GD patients treated with antithyroid medication develop HT, thus suggesting a possible conversion or shift from GD to HT disease. DES-Tcell found miR-4442 links to both GD and HT, and that miR-4442 possibly targets the autoimmune disease risk factor CD6, which provides potential new knowledge derived through the use of DES-Tcell. According to our understanding, DES-Tcell is the first KB dedicated to exploring T-cell-relevant information via literature-mining, data-mining, and topic-specific dictionaries.

show abstract

“…Some literatures have shown that ceRNA network participates in the occurrence of MDR in cancers, including nasopharyngeal carcinoma ( Wang et al, 2020 ) and AML ( Yu et al, 2020 ). However, except for one paper ( Zhang et al, 2019 ), there is no other report on ceRNA regulatory network and its role in MDR-CML.…”

Section: Discussionmentioning

confidence: 99%

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Liu

Wang

et al. 2021

PeerJ

View full text Add to dashboard Cite

Background Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. Methods The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay. Results The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC50) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC50 of doxorubicin. Conclusions The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.

show abstract

LncRNA MEG3 contributes to drug resistance in acute myeloid leukemia by positively regulating ALG9 through sponging miR‐155

Cited by 41 publications

References 21 publications

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

miR155 Enhances Autophagy by Reducing MBD5 and METTL3 in Human Liver Cancer Stem Cells

DES-Tcell is a knowledgebase for exploring immunology-related literature

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR

Contact Info

Product

Resources

About