PRMT6 promotes endometrial cancer via AKT/mTOR signaling and indicates poor prognosis

Jiang, Nan; Li, Qiuli; Pan, Wenwei; Li, Jinhui; Zhang, Meifang; Cao, Tiefeng; Su, Shu-Guang; Shen, Huimin

doi:10.1016/j.biocel.2019.105681

Cited by 33 publications

(31 citation statements)

References 31 publications

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“…Previous studies demonstrated that PRMT6 can regulate the activation of PI3K/AKT signaling pathway 18 , 19 and the PI3K/AKT pathway plays an important role in regulating the osteogenesis of MSCs 20 . In addition, KEGG pathway enrichment analyses found that the gene-enriched pathway contains the PI3K/AKT pathway (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

The N6-methyladenosine demethylase ALKBH5 negatively regulates the osteogenic differentiation of mesenchymal stem cells through PRMT6

Wang

et al. 2021

Cell Death Dis

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N6-methyladenosine (m6A) modification is widespread in messenger RNAs and increasing evidence suggests the crucial roles of m6A in cell differentiation and tissue development. However, whether m6A modulates the osteogenic differentiation of mesenchymal stem cells (MSCs) has not been fully elucidated. Here we show that conditional knockout of the demethylase Alkbh5 in bone marrow MSCs strengthened bone mass in mice. Loss- and gain-of-function studies demonstrated that ALKBH5 negatively regulates the osteogenic differentiation of MSCs in vitro. At a mechanistic level, meRIP-seq and RNA-seq in MSCs following knockdown of ALKBH5 revealed changes in transcripts of PRMT6 containing consensus m6A motifs required for demethylation by ALKBH5. Furthermore, we found that ALKBH5 accelerates the degradation rate of PRMT6 mRNA in an m6A-dependent manner, and that the ALKBH5-PRMT6 axis regulates the osteogenesis of MSCs, mainly through activation of the PI3K/AKT pathway. Thus, our work reveals a different facet of the novel ALKBH5-PRMT6 axis that modulates the osteogenic differentiation of MSCs, which can serve as a target to improve the clinical use of MSCs.

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Section: Resultsmentioning

confidence: 99%

The N6-methyladenosine demethylase ALKBH5 negatively regulates the osteogenic differentiation of mesenchymal stem cells through PRMT6

Wang

et al. 2021

Cell Death Dis

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“…HOXD10 was found to act as a tumor suppressor, which inhibited the development of esophageal squamous cell carcinoma through the PI3K/AKT/mTOR pathway [ 21 ], and in another study, expression of the AKT/mTOR signaling pathway was associated with the progression of EC [ 36 ]. In this study, we found that overexpression of miR-501 can inhibit expression of HOXD10 and increase expression of the AKT/mTOR pathway, which was in accordance with the previous studies.…”

Section: Discussionmentioning

confidence: 99%

MiR-501 promotes tumor proliferation and metastasis by targeting HOXD10 in endometrial cancer

et al. 2021

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Background Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure. Methods The expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. Results In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway. Conclusions MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer.

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“…ASH2L, a component of the histone methyltransferase complex, is also overexpressed in EC. High expression of ASH2L is associated with poor prognosis, whereas ASH2L knockdown suppressed EC cell growth by regulating PAX2 transcription and altering the levels of H3K4me3 and H3K27me3 [91][92][93][94][95]. LSD1, also known as KDM1A, has higher expression levels in EC than in normal endometrium, and is associated with poor prognosis [92][93][94].…”

Section: Histone Methylation and Ecmentioning

confidence: 99%

Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications

Inoue¹,

Sone²,

Toyohara³

et al. 2021

IJMS

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Endometrial cancer is one of the most frequently diagnosed gynecological malignancies worldwide. However, its prognosis in advanced stages is poor, and there are only few available treatment options when it recurs. Epigenetic changes in gene function, such as DNA methylation, histone modification, and non-coding RNA, have been studied for the last two decades. Epigenetic dysregulation is often reported in the development and progression of various cancers. Recently, epigenetic changes in endometrial cancer have also been discussed. In this review, we give the main points of the role of DNA methylation and histone modification in endometrial cancer, the diagnostic tools to determine these modifications, and inhibitors targeting epigenetic regulators that are currently in preclinical studies and clinical trials.

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PRMT6 promotes endometrial cancer via AKT/mTOR signaling and indicates poor prognosis

Cited by 33 publications

References 31 publications

The N6-methyladenosine demethylase ALKBH5 negatively regulates the osteogenic differentiation of mesenchymal stem cells through PRMT6

The N6-methyladenosine demethylase ALKBH5 negatively regulates the osteogenic differentiation of mesenchymal stem cells through PRMT6

MiR-501 promotes tumor proliferation and metastasis by targeting HOXD10 in endometrial cancer

Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications

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