Emerging Role of RNA m5C Modification in Cardiovascular Diseases

Balachander, Kannan; Priyadharsini, J. Vijayashree; Roy, Anitha; Paramasivam, Arumugam

doi:10.1007/s12265-022-10336-8

Cited by 10 publications

(8 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulating evidence has revealed associations between abnormal m5C modification and numerous diseases and disease-related processes, such as cancers, cardiovascular diseases, neurological disorders, and inflammation (17,(35)(36)(37)(38). However, little is known about the precise correlations between RNA m5C modification and PNI in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

Zheng,

Hu,

Lin

et al. 2024

Sci. Transl. Med.

View full text Add to dashboard Cite

Perineural invasion (PNI) is a biological characteristic commonly observed in pancreatic cancer. Although PNI plays a key role in pancreatic cancer metastasis, recurrence, and poor postoperative survival, its mechanism is largely unclarified. Clinical sample analysis and endoscopic ultrasonographic elasticity scoring indicated that cancer-associated fibroblasts (CAFs) were closely related to the occurrence of PNI. Furthermore, CAF-derived extracellular vesicles (EVs) were involved in PNI in dorsal root ganglion coculture and mouse sciatic nerve models. Next, we demonstrated that CAFs promoted PNI through extracellular vesicle transmission of PNI-associated transcript (PIAT). Mechanistically, PIAT specifically bound to YBX1 and blocked the YBX1-Nedd4l interaction to inhibit YBX1 ubiquitination and degradation. Furthermore, PIAT enhanced the binding of YBX1 and PNI-associated mRNAs in a 5-methylcytosine (m5C)–dependent manner. Mutation of m5C recognition motifs in YBX1 or m5C sites in downstream target genes reversed PIAT-mediated PNI. Consistent with these findings, analyses using a KPC mouse model demonstrated that the PIAT/YBX1 axis enhanced PNI through m5C modification. Clinical data suggested that the PIAT expression in the serum EVs of patients with pancreatic cancer was associated with the degree of neural invasion and prognosis. Our study revealed the important role of the PIAT/YBX1 signaling axis in the tumor microenvironment (TME) in promoting tumor cell PNI and provided a new target for precise interference with CAFs and RNA methylation in the TME to suppress PNI in pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

Zheng,

Hu,

Lin

et al. 2024

Sci. Transl. Med.

View full text Add to dashboard Cite

show abstract

“…Heterogenous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is also suggested to regulate cardiac homeostasis and hypertrophy via N6 methyladenosine mRNA methylase (METTL3) and m6A switch recognition and alternative splicing events ( Qin et al, 2020 ; Fan and Hu, 2022 ). RBPs also contribute to the regulation of RNA m5C methylation, dysregulation of which is closely associated with CVD ( Balachander et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

RNA binding proteins as mediators of pathological cardiac remodeling

Acharya,

Parkins,

Tranter

2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

RNA binding proteins (RBPs) play a central in the post-transcriptional regulation of gene expression, which can account for up to 50% of all variations in protein expression within a cell. Following their binding to target RNAs, RBPs most typically confer changes in gene expression through modulation of alternative spicing, RNA stabilization/degradation, or ribosome loading/translation rate. All of these post-transcriptional regulatory processes have been shown to play a functional role in pathological cardiac remodeling, and a growing body of evidence is beginning to identify the mechanistic contribution of individual RBPs and their cardiac RNA targets. This review highlights the mechanisms of RBP-dependent post-transcriptional gene regulation in cardiomyocytes and fibroblasts and our current understanding of how RNA binding proteins functionally contribute to pathological cardiac remodeling.

show abstract

“…RNA methylation plays a key role in various biological processes, such as nuclear RNA export capacity, RNA stability enhancement, RNA shearing and RNA-protein interaction regulation. 7 Abnormal RNA methylation levels are associated with tumors, 8 cardiovascular system diseases 9 and neurological diseases. 10 There are different types of RNA methylation, comprising N1-methyl-adenosine (m 1 A), m 5 C, N6-methyl-adenosine (m 6 A), 7-methyl-guanosine (m 7 G) and Um.…”

Section: Introductionmentioning

confidence: 99%

Function of m ⁵ C RNA methyltransferase NOP2 in high-grade serous ovarian cancer

Yang,

Zhou,

Zhang

et al. 2023

Cancer Biology & Therapy

View full text Add to dashboard Cite

RNA methyltransferase nucleolar protein p120 (NOP2), commonly referred to as NOP2/Sun RNA methyltransferase family member 1 (NSUN1), is involved in cell proliferation and is highly expressed in various cancers. However, its role in high-grade serous ovarian cancer (HGSOC) remains unclear. Our study investigated the expression of NOP2 in HGSOC tissues and normal fimbria tissues, and found that NOP2 was significantly upregulated in HGSOC tissues. Our experiments showed that NOP2 overexpression promoted cell proliferation in vivo and in vitro and increased the migration and invasion ability of HGSOC cells in vitro . Furthermore, we identified Rap guanine nucleotide exchange factor 4 (RAPGEF4) as a potential downstream target of NOP2 in HGSOC. Finally, our findings suggest that the regulation of NOP2 and RAPGEF4 may depend on m 5 C methylation levels.

show abstract

Emerging Role of RNA m5C Modification in Cardiovascular Diseases

Cited by 10 publications

References 50 publications

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

RNA binding proteins as mediators of pathological cardiac remodeling

Function of m ⁵ C RNA methyltransferase NOP2 in high-grade serous ovarian cancer

Contact Info

Product

Resources

About

Emerging Role of RNA m5C Modification in Cardiovascular Diseases

Cited by 10 publications

References 50 publications

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

Extracellular vesicle–packaged PIAT from cancer-associated fibroblasts drives neural remodeling by mediating m5C modification in pancreatic cancer mouse models

RNA binding proteins as mediators of pathological cardiac remodeling

Function of m 5 C RNA methyltransferase NOP2 in high-grade serous ovarian cancer

Contact Info

Product

Resources

About

Function of m ⁵ C RNA methyltransferase NOP2 in high-grade serous ovarian cancer