Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis

Wang, Airong; Chen, Yufei; Shi, Luyao; Li, Mengya; Wang, Shujuan; Wang, Chong

doi:10.1186/s12967-022-03456-x

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…Li et al showed that METTL3, through methylating modifications on integrin alpha 4 (ITGA4) mRNA, increases ITGA4 protein expression and promotes homing/engraftment of AML cells, thereby mediating chemoresistance [ 141 ]. Wang also reported that the tumour suppressor genes MEG3 and miRNA-493-5p, which are lowly expressed in AML cells, upregulate the METTL3/Myc axis, thereby promoting chemoresistance in AML cells [ 142 ]. But at the same time, there are some studies that expressed the opposite point.…”

Section: Potential Of M 6 a In Cancer Therapymentioning

confidence: 99%

Small molecule inhibitors targeting m6A regulators

Feng,

Wu,

et al. 2024

J Hematol Oncol

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As the most common form of epigenetic regulation by RNA, N6 methyladenosine (m6A) modification is closely involved in physiological processes, such as growth and development, stem cell renewal and differentiation, and DNA damage response. Meanwhile, its aberrant expression in cancer tissues promotes the development of malignant tumors, as well as plays important roles in proliferation, metastasis, drug resistance, immunity and prognosis. This close association between m6A and cancers has garnered substantial attention in recent years. An increasing number of small molecules have emerged as potential agents to target m6A regulators for cancer treatment. These molecules target the epigenetic level, enabling precise intervention in RNA modifications and efficiently disrupting the survival mechanisms of tumor cells, thus paving the way for novel approaches in cancer treatment. However, there is currently a lack of a comprehensive review on small molecules targeting m6A regulators for anti-tumor. Here, we have comprehensively summarized the classification and functions of m6A regulators, elucidating their interactions with the proliferation, metastasis, drug resistance, and immune responses in common cancers. Furthermore, we have provided a comprehensive overview on the development, mode of action, pharmacology and structure–activity relationships of small molecules targeting m6A regulators. Our aim is to offer insights for subsequent drug design and optimization, while also providing an outlook on future prospects for small molecule development targeting m6A.

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Section: Potential Of M 6 a In Cancer Therapymentioning

confidence: 99%

Small molecule inhibitors targeting m6A regulators

Feng,

Wu,

et al. 2024

J Hematol Oncol

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“…MDR and disease relapse remain major obstacles in the treatment of acute myeloid leukemia (AML), which is a highly invasive malignant hematopoietic system disease [106,107]. Recently, Wang and colleagues found that the miR-493-5p-dependent suppression of methyltransferase-like 3 (METTL3) increases the sensitivity of AML cells to the chemotherapeutic drug arabinocytosine [108]. There is evidence that miRNAs also contribute to increased chemoresistance in AML.…”

Section: The Role Of Mirnas In Cancer Therapy Resistancementioning

confidence: 99%

Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

Bayraktar

Oztatlici

et al. 2023

ncRNA

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Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such as anti-miRS), these therapeutics have shown promise in preclinical settings. Some miRNA-targeted therapeutics have been extended to clinical development, such as the mimic of miRNA-34 for treating cancer. Here, we discuss insights into the role of miRNAs and other non-coding RNAs in tumorigenesis and resistance and summarize some recent successful systemic delivery approaches and recent developments in miRNAs as targets for anticancer drug development. Furthermore, we provide a comprehensive overview of mimics and inhibitors that are in clinical trials and finally a list of clinical trials based on miRNAs.

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“…MEG3 positively regulated miR-493-5p expression which directly targeted METTL3. 144 Moreover, it was found that LINC00470 positively regulated m6A modification of PTEN mRNA via METTL3 and inhibited PTEN expression, thus leading to the suppression of autophagy and the promotion of chemoresistance in AML cells. 145 Glioblastoma multiforme (GBM) is the most common form of brain cancer and one of the most aggressive cancers found in humans, with a survival rate of 5.5% at five years.…”

Section: Other Cancermentioning

confidence: 99%

“…MEG3 positively regulated miR‐493‐5p expression which directly targeted METTL3. 144 Moreover, it was found that LINC00470 positively regulated m6A modification of PTEN mRNA via METTL3 and inhibited PTEN expression, thus leading to the suppression of autophagy and the promotion of chemoresistance in AML cells. 145 …”

Section: Interaction Between M6a Modification and Lncrna In Cancer Dr...mentioning

confidence: 99%

New insights into the interaction between m6A modification and lncRNA in cancer drug resistance

Jin,

Fan

2023

Cell Proliferation

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Drug resistance is perhaps the greatest obstacle in improving outcomes for cancer patients, leading to recurrence, progression and metastasis of various cancers. Exploring the underlying mechanism worth further study. N6‐methyladenosine (m6A) is the most common RNA modification found in eukaryotes, playing a vital role in RNA translation, transportation, stability, degradation, splicing and processing. Long noncoding RNA (lncRNA) refers to a group of transcripts that are longer than 200 nucleotides (nt) and typically lack the ability to code for proteins. LncRNA has been identified to play a significant role in regulating multiple aspects of tumour development and progression, including proliferation, metastasis, metabolism, and resistance to treatment. In recent years, a growing body of evidence has emerged, highlighting the crucial role of the interplay between m6A modification and lncRNA in determining the sensitivity of cancer cells to chemotherapeutic agents. In this review, we focus on the recent advancements in the interaction between m6A modification and lncRNA in the modulation of cancer drug resistance. Additionally, we aim to explore the underlying mechanisms involved in this process. The objective of this review is to provide valuable insights and suggest potential future directions for the reversal of chemoresistance in cancer.

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Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis

Cited by 21 publications

References 35 publications

Small molecule inhibitors targeting m6A regulators

Small molecule inhibitors targeting m6A regulators

Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update

New insights into the interaction between m6A modification and lncRNA in cancer drug resistance

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