Identification and characterization of N6‐methyladenosine modification of circRNAs in glioblastoma

Zhang, Yuhao; Geng, Xiuchao; Xu, Jintao; Li, Qiang; Hao, Liangchao; Zeng, Zhaomu; Xiao, Menglin; Song, Jia; Liu, Fulin; Fang, Chuan; Wang, Hong

doi:10.1111/jcmm.16750

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…As shown in Figure 1E , when we counted the number of m7G peaks for each mRNA in the two groups, we found that most methylated mRNAs in HL60 and HL60/MX2 cells had only one m7G peak (70.8% and 74.3%, respectively). In the two groups, approximately 20% of the genes recorded two m7G peaks, and less than 10% of the genes contained more than three m7G peaks, which was consistent with previous studies of methylation in other diseases ( 22 , 23 ). We performed a statistical analysis of the length of the methylation peak, and our results revealed that there was no statistically significant difference between the two groups.…”

Section: Resultssupporting

confidence: 92%

Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

2022

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Acute myeloid leukemia (AML) is an aggressive hematological tumor caused by the malignant transformation of myeloid progenitor cells. Although intensive chemotherapy leads to an initial therapeutic response, relapse due to drug resistance remains a significant challenge. In recent years, accumulating evidence has suggested that post-transcriptional methylation modifications are strongly associated with tumorigenesis. However, the mRNA profile of m7G modification in AML and its role in drug-resistant AML are unknown. In this study, we used MeRIP-seq technology to establish the first transcriptome-wide m7G methylome profile for AML and drug-resistant AML cells, and differences in m7G between the two groups were analyzed. In addition, bioinformatics analysis was conducted to explore the function of m7G-specific methylated transcripts. We found significant differences in m7G mRNA modification between AML and drug-resistant AML cells. Furthermore, bioinformatics analysis revealed that differential m7G-modified mRNAs were associated with a wide range of cellular functions. Importantly, down-methylated m7G modification was significantly enriched in ABC transporter-related mRNAs, which are widely recognized to play a key role in multidrug resistance. Our results provide new insights into a novel function of m7G methylation in drug resistance progression of AML.

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Section: Resultssupporting

confidence: 92%

Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

2022

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“…Although surgical techniques and radiochemotherapy regimens have been improving in recent decades, the survival rate of glioma has not increased as expected [ 29 – 32 ]. Chemoresistance is a major cause of chemotherapy failure in glioma patients.…”

Section: Discussionmentioning

confidence: 99%

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma

et al. 2022

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Exosome-mediated delivery of circular RNAs (circRNAs) is implicated in cancer progression. However, the role of exosomal circRNAs in the chemotherapy resistance of tumours remains poorly understood. Here we identified a novel circRNA, circWDR62. It was found that circWDR62 expression was upregulated in TMZ-resistant glioma cells and TMZ-resistant glioma cell-derived exosomes compared with their controls by using high-throughput microarray analysis and quantitative real-time polymerase chain reaction, and high circWDR62 expression was associated with poor prognosis of glioma. Functionally, downregulation of circWDR62 expression could significantly inhibit the TMZ resistance and malignant progression of glioma. Further mechanistic studies showed that circWDR62 plays a role by sponging miR-370-3p as a competing endogenous RNA. Rescue experiments confirmed that MGMT is the downstream target of the circWDR62/miR-370-3p axis in glioma. In addition, circWDR62 could be transported between TMZ-resistant and TMZ-sensitive glioma cells via exosomes. Exosomal circWDR62 from TMZ-resistant cells conferred TMZ resistance in recipient sensitive cells while also enhancing the proliferation, migration and invasion of these cells. A series of clinical and in vivo trials corroborated that exosomal circWDR62 could promote TMZ chemoresistance and malignant progression of glioma. Our results demonstrate for the first time that exosome-mediated delivery of circWDR62 can promote TMZ resistance and malignant progression via targeting of the miR-370-3p/MGMT axis in vitro and in vivo in glioma, providing a new therapeutic strategy. Moreover, exosomal circWDR62 in human serum may serve as a promising therapeutic target and prognostic marker for glioma therapy.

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“…In recent years, mRNA modi cation, especially m6A, has drawn lots of attention. m6A has been indicated involving in various biological processes, such as cell proliferation, invasion, metastasis, immune system evasion, stress response, tumorigenesis, and so on [36][37][38][39][40][41][42][43][44]. m5C, as a new modi cation factor, also is related to tumor translation, occurrence and metastasis.…”

Section: Discussionmentioning

confidence: 99%

5-methylcytosine profile of mRNA in breast cancer brain metastasis

Cai

Jiang

Zhang

et al. 2022

Preprint

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Background: 5-methylcytosine (m5C) modification is involved in various physiological process of diseases. Great amount of research has been conducted to reveal the m5C profile, while the m5C profile of mRNA in breast cancer brain metastasis is unknown. Materials & methods: We performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) to identify the m5C profile of mRNA in breast cancer brain metastasis cells (231-BR cells). Results: mRNA m5C profiles showed difference in peak numbers, length and modification level between 231-BR cells and its parental nonspecific metastatic MDA-MB-231 cells. Compared with the control cells, we gained 1048 higher and 1866 lower methylation peaks in 231-BR cells. The most significant differentially methylated genes in m5C level included NSCN7, YBX3, SHANK1, MMP9, and LCN2. In addition, through GO and KEGG analysis, differently m5C methylated genes were chiefly engaged in the pathways of cancer cell focal adhesion, basal carcinoma, and endocytosis. Finally, the conjoint analysis of mRNA expression and RNA m5C modification was performed and that there are 346 genes showed coefficient changes. Conclusion: This study may comply a novel vision as a basis for subsequent mechanism research of breast cancer brain metastasis.

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Identification and characterization of N6‐methyladenosine modification of circRNAs in glioblastoma

Cited by 12 publications

References 42 publications

Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

Transcriptome Profiling of N7-Methylguanosine Modification of Messenger RNA in Drug-Resistant Acute Myeloid Leukemia

Exosomal circWDR62 promotes temozolomide resistance and malignant progression through regulation of the miR-370-3p/MGMT axis in glioma

5-methylcytosine profile of mRNA in breast cancer brain metastasis

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