Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression

Du, Chen; Lv, Caihong; Feng, Yue; Yu, Siwen

doi:10.1186/s13046-020-01735-3

Cited by 70 publications

(64 citation statements)

References 22 publications

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“…Previous studies revealed that m6A mark acted as a key post-transcriptional modification that promoted the initiation of miRNA biogenesis [52] . Moreover, H3K4me3 demethylase, bound to the miRNA promoter, which led to inhibition of its transcription and expression [53] . SnoRNAs, involving in ribosome biogenesis and RNA modification, acted as endogenous sponges that regulate miRNA expression [54] .…”

Section: Discussionmentioning

confidence: 99%

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

et al. 2021

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Background: Osteoarthritis (OA), a disease with whole-joint damage and dysfunction, is the leading cause of disability worldwide. The progressive loss of hyaline cartilage extracellular matrix (ECM) is considered as its hallmark, but its exact pathogenesis needs to be further clarified. MicroRNA(miRNA) contributes to OA pathology and may help to identify novel biomarkers and therapies against OA. Here we identified miR-214À3p as an important regulator of OA. Methods: qRT-PCR and in situ hybridization were used to detect the expression level of miR-214À3p. The function of miR-214À3p in OA, as well as the interaction between miR-214À3p and its downstream mRNA target (IKBKB), was evaluated by western blotting, immunofluorescence, qRT-PCR and luciferase assay. Mice models were introduced to examine the function and mechanism of miR-214À3p in OA in vivo. Findings: In our study, we found that miR-214À3p, while being down-regulated in inflamed chondrocytes and OA cartilage, regulated ECM metabolism and cell apoptosis in the cartilage. Mechanically, the protective effect of miR-214À3p downregulated the IKK-b expression and led to the dysfunction of NF-kB signaling pathway. Furthermore, intra-articular injection of miR-214À3p antagomir in mice joints triggered spontaneous cartilage loss while miRNA-214À3p agomir alleviated OA in the experimental mouse models. Interpretation: Decreased miR-214À3p activates the NF-kB signaling pathway and aggravates OA development through targeting IKKb, suggesting miR-214À3p may be a novel therapeutic target for OA.

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Section: Discussionmentioning

confidence: 99%

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

et al. 2021

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“…In addition, KDM5A mediates reduction in methylated H3K4 and thus decreases the levels of two tumor suppression and differentiation genes KLF4 and E-cadherin , which lead to the malignancy of PCa [ 97 ]. KDM5A is also capable of promoting PCa progression via the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis [ 98 ].…”

Section: Kdm5a In Human Cancermentioning

confidence: 99%

The emerging role of KDM5A in human cancer

Yang

Zhu

et al. 2021

J Hematol Oncol

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Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field.

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“…miR-145 was implicated in the regulation of m6A levels of HCC by targeting YTHDF2 [57]. Furthermore, decreased expression of miR-495 and miR-493-3p leaded to upregulated YTHDF2 and enhanced proliferation and invasion in prostate cancer [58,59]. Therefore, we nally performed differential microRNA expression analysis and observed that YTHDF2 was the target of miR-205, which was decreased in MM and negatively correlated with YTHDF2.…”

Section: Discussionmentioning

confidence: 97%

Expression Status and Prognostic Roles of m6A-related Genes in Multiple Myeloma: YTHDF2 as the independent prognostic factor

Li¹,

Shen²,

Wu³

et al. 2021

Preprint

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Background: N6-methyladenosine is the most abundant RNA modification, which plays a prominent role in multiple biology processes, including tumorigenesis. Multiple myeloma (MM) is the second most frequent hematological cancer. However, the expression status and value of m6A-related genes in multiple myeloma remain elusive.Methods: m6A-related gene expression data and clinical information of MM patients were obtained from the Gene Expression Omnibus (GEO) database. Based on differentially expressed analysis, protein-protein interaction (PPI) analysis, Pearson correlation analysis, Kaplan-Meier survival analysis and Cox regression analysis, the prognostic m6A-associated genes were identified. The receiver operation characteristic (ROC) curves were used to verify the prognostic and diagnostic efficiency. The molecular mechanisms were investigated by differentially expressed mRNA and microRNA analyses with the help of online database ENCORI and POSTAR.Results: Among 22 m6A-related genes, HNRNPC, RBM15B, RBM15, YTHDF3, YTHDF2, HNRNPA2B1 and IGF2BP2 were significantly upregulated, while ZC3H13, FTO, IGF2BP3, ALKBH5 and YTHDC1 were significantly downregulated in MM patients. The high expression of HNRNPC, HNRNPA2B1, YTHDF2 and the low expression of ZC3H13 were associated with adverse survival. Furthermore, the expression level of YTHDF2 was the independent prognostic factor of MM. ROC curves suggested the great prediction performance for MM patients. Differentially expressed mRNA and microRNA analyses indicated the probable involvement of miR-205/YTHDF2/EGR1 axis.Conclusions: Our study first systematically analyzed the expression status of m6A-related genes in multiple myeloma, identified HNRNPC, HNRNPA2B1, YTHDF2 and ZC3H13 that could be the potential prognostic biomarkers, especially YTHDF2, which may be implicated in the miR-205/YTHDF2/EGR1 axis.

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Activation of the KDM5A/miRNA-495/YTHDF2/m6A-MOB3B axis facilitates prostate cancer progression

Cited by 70 publications

References 22 publications

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression

The emerging role of KDM5A in human cancer

Expression Status and Prognostic Roles of m6A-related Genes in Multiple Myeloma: YTHDF2 as the independent prognostic factor

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