Role of RNA methylation in the regulation of pancreatic cancer stem cells (Review)

Tsuji, Yoshiko; Hara, Tomoaki; Meng, Songdong; Sato, Hiromichi; Arao, Yasuko; Ofusa, Ken; Ishii, Hideshi

doi:10.3892/ol.2023.13922

Cited by 3 publications

(1 citation statement)

References 95 publications

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“… 9 MeRIP‐seq has been performed on various cancer cell tumors, and m6A has been found to be associated with malignant transformation of cancer. 10 It has been reported that inhibition of expression of METTL14 (m6A methyltransferase) and ALKBH5 (demethylase) in human breast cancer cell lines inhibits cancer growth and invasion. 11 The 3′ UTR of homeobox containing 1 (HMBOX1) mRNA is modified with m6A by METTL3, and its translation is repressed in prostate cancer cell LNCaP compared with epithelial cell RWPE‐1, a normal cell line, and telomere length and p53 signaling are aberrant.…”

Section: Introductionmentioning

confidence: 99%

High N6‐methyladenosine‐activated TCEAL8 mRNA is a novel pancreatic cancer marker

Hara,

Meng,

Sato

et al. 2024

Cancer Science

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N6‐methyladenosine (m6A) is an RNA modification involved in RNA processing and widely found in transcripts. In cancer cells, m6A is upregulated, contributing to their malignant transformation. In this study, we analyzed gene expression and m6A modification in cancer tissues, ducts, and acinar cells derived from pancreatic cancer patients using MeRIP‐seq. We found that dozens of RNAs highly modified by m6A were detected in cancer tissues compared with ducts and acinar cells. Among them, the m6A‐activated mRNA TCEAL8 was observed, for the first time, as a potential marker gene in pancreatic cancer. Spatially resolved transcriptomic analysis showed that TCEAL8 was highly expressed in specific cells, and activation of cancer‐related signaling pathways was observed relative to TCEAL8‐negative cells. Furthermore, among TCEAL8‐positive cells, the cells expressing the m6A‐modifying enzyme gene METTL3 showed co‐activation of Notch and mTOR signaling, also known to be involved in cancer metastasis. Overall, these results suggest that m6A‐activated TCEAL8 is a novel marker gene involved in the malignant transformation of pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

High N6‐methyladenosine‐activated TCEAL8 mRNA is a novel pancreatic cancer marker

Hara,

Meng,

Sato

et al. 2024

Cancer Science

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Insights into the mechanisms driven by H3K4 KMTs in pancreatic cancer

LaRue-Nolan,

Raja Arul,

Sigafoos

et al. 2024

Biochemical Journal

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Pancreatic cancer is a malignancy arising from the endocrine or exocrine compartment of this organ. Tumors from exocrine origin comprise over 90% of all pancreatic cancers diagnosed. Of these, pancreatic ductal adenocarcinoma (PDAC) is the most common histological subtype. The five-year survival rate for PDAC ranged between 5 and 9% for over four decades, and only recently saw a modest increase to ∼12–13%, making this a severe and lethal disease. Like other cancers, PDAC initiation stems from genetic changes. However, therapeutic targeting of PDAC genetic drivers has remained relatively unsuccessful, thus the focus in recent years has expanded to the non-genetic factors underlying the disease pathogenesis. Specifically, it has been proposed that dynamic changes in the epigenetic landscape promote tumor growth and metastasis. Emphasis has been given to the re-organization of enhancers, essential regulatory elements controlling oncogenic gene expression, commonly marked my histone 3 lysine 4 monomethylation (H3K4me1). H3K4me1 is typically deposited by histone lysine methyltransferases (KMTs). While well characterized as oncogenes in other cancer types, recent work has expanded the role of KMTs as tumor suppressor in pancreatic cancer. Here, we review the role and translational significance for PDAC development and therapeutics of KMTs.

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Recent advances in noncoding RNA modifications of gastrointestinal cancer

Hara,

Meng,

Arao

et al. 2024

Cancer Science

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Elucidating the mechanisms underlying cancer development and proliferation is important for the development of therapeutic methods for the complete cure of cancer. In particular, the identification of diagnostic markers for early detection and new therapeutic strategies for refractory gastrointestinal cancers are needed. Various abnormal phenomena occur in cancer cells, such as functional changes of proteins, led by genomic mutations, and changes in gene expression due to dysregulation of epigenetic regulation. This is no exception for noncoding RNA (ncRNA), which do not encode proteins. Recent reports have revealed that microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) are deeply involved in cancer progression. These ncRNAs have attracted attention as gene expression regulatory molecules. Recent advances in technology have made it possible not only to read DNA and RNA sequences but also to study the modification state of each base. In particular, comprehensive analysis of N6‐methyladenosine (m6A) has been performed by many research groups, with multiple studies reporting that m6A modifications of specific genes are associated with cancer progression. Based on the above, this review examines how ncRNA modifications are related to cancer progression in gastrointestinal cancers such as colorectal and pancreatic cancer. We also discuss enzyme inhibitors that have been reported to have drug discovery potential targeting m6A modifications. By utilizing the new perspective of ncRNA modification, we may be able to accumulate knowledge on the molecular biology of cancer and contribute to human health through diagnosis and treatment.

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Role of RNA methylation in the regulation of pancreatic cancer stem cells (Review)

Cited by 3 publications

References 95 publications

High N6‐methyladenosine‐activated TCEAL8 mRNA is a novel pancreatic cancer marker

High N6‐methyladenosine‐activated TCEAL8 mRNA is a novel pancreatic cancer marker

Insights into the mechanisms driven by H3K4 KMTs in pancreatic cancer

Recent advances in noncoding RNA modifications of gastrointestinal cancer

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