MicroRNA signatures associated with lymph node metastasis in intramucosal gastric cancer

Kim, Seokhwi; Bae, Won Jung; Ahn, Ji Mi; Heo, Jin Hyung; Kim, Kyoung‐Mee; Choi, Kyeong Woon; Sung, Chang Ohk; Lee, Dakeun

doi:10.1038/s41379-020-00681-x

Cited by 30 publications

(21 citation statements)

References 53 publications

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“…Bioinformatics tools identified miR-181d-5p as a potential target of circ_0045861. Recently, miR-181d-5p has been reported to be involved in the development of a variety of tumors (25)(26)(27)(28). MiR-181d-5p-containing exosomes derived from cancer-associated fibroblasts can promote epithelial-mesenchymal transition by regulating CDX2/HOXA5 in breast cancer cells (29).…”

Section: Discussionmentioning

confidence: 99%

Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis

Yin

Zhao

et al. 2021

Ann Transl Med

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Background: Ureteropelvic junction obstruction (UPJO) is one of the most common causes of hydronephrosis in children. This study explored the effects and the regulatory mechanisms of the circular RNA (circRNA) hsa_circRNA_0045861 (circRNA_0045861) in UPJO.Methods: RNA sequencing was used to identify the differentially expressed circRNAs in UPJO. The effects of circRNA_0045861 on renal cell apoptosis was investigated by flow cytometry and Western blot analysis. Furthermore, we used bioinformatics methods to predict the possible target genes of circRNA_0045861.Fluorescence in-situ hybridization and dual-luciferase reporter assays were performed to validate the target genes of circRNA_0045861. Finally, we evaluated the effects of circRNA_0045861 target gene miR-181d-5p on UPJO-induced renal fibrosis in vivo.Results: RNA sequencing identified 63 upregulated and 64 downregulated circRNAs in UPJO patients.The expression of circRNA_0045861 was significantly elevated in kidney damage both in vivo and in vitro.Silencing circ_0045861 inhibited transforming growth factor (TGF)-β1-induced apoptosis in vitro in human kidney 2 (HK-2) cells. Furthermore, circ_0045861 was shown to directly interact with the microRNA miR-181d-5p and regulate the expression of sirtuin 1 (SIRT1), thereby promoting the progression of apoptosis and renal injury. In addition, overexpression of miR-181d-5p inhibited cell apoptosis and renal fibrosis in a mouse model through downregulating the SIRT1/p53 pathway.Conclusions: Circ_0045861 may be a novel candidate circRNA in the pathogenesis of UPJO by acting as a pro-apoptotic factor via the miR-181d-5p/SIRT1 axis.

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Section: Discussionmentioning

confidence: 99%

Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis

Yin

Zhao

et al. 2021

Ann Transl Med

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“…The substitution of C or T alleles in this polymorphism showed that the former is expressed 1.49-fold more than the latter allele, supporting the association of this polymorphism with GC. The reduced risk of rs14396919 in miR-3175 is according to Kim et al [ 25 ] who identified miR-3175 as a member of a miRNA signature associated with lymph node metastasis in GC at early stages (intramucosal stage). In other tumors such glioma and prostate, miR-3175 promotes cell proliferation, invasion and apoptosis [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population

Landeros

Corvalán

Musleh

et al. 2021

IJMS

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Gastric cancer (GC) is the fifth leading cause of cancer deaths in the world, with variations across geographical regions and ethnicities. Emerging evidence indicates that miRNA expression is dysregulated in GC and its polymorphisms may contribute to these variations, which has yet to be explored in Latin American populations. In a case-control study of 310 GC patients and 311 healthy donors from Chile, we assessed the association of 279 polymorphisms in 242 miRNA genes. Two novel polymorphisms were found to be associated with GC: rs4822739:C>G (miR-548j) and rs701213:T>C (miR-4427). Additionally, rs1553867776:T>TCCCCA (miR-4274) and rs12416605:C>T (miR-938) were associated with intestinal-type GC, and rs4822739:C>G (miR-548j) and rs1439619:T>G (miR-3175) with TNM I-II stage. The polymorphisms rs6149511:T> TGAAGGGCTCCA (miR-6891), rs404337:G>A (miR-8084), and rs1439619:T>G (miR-3175) were identified among H.pylori-infected GC patients and rs7500280:T>C (miR-4719) and rs1439619:T>G (miR-3175) were found among H. pylori cagPAI+ infected GC cases. Prediction analysis suggests that seven polymorphisms could alter the secondary structure of the miRNA, and the other one is located in the seed region of miR-938. Targets of miRNAs are enriched in GC pathways, suggesting a possible biological effect. In this study, we identified seven novel associations and replicated one previously described in Caucasian population. These findings contribute to the understanding of miRNA genetic polymorphisms in the GC pathogenesis.

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“…Yuan et al published a second study reporting the formation and folding of a stable parallel rG4 in miR-3620-5p in physiological conditions by using a set of biophysical techniques such as ESI-MS, CD, NMR, and SPR [73] (Figure 9). This miR is reported to be associated with different kinds of cancers, such as gastric cancer and metastasis [79]. Additionally, the same authors concluded that sanguinarine, a natural alkaloid used in traditional Chinese medicine, binds and stabilizes the rG4 in miR-3620-5p [73].…”

Section: Rg4s In Mirnasmentioning

confidence: 91%

Ligands as Stabilizers of G-Quadruplexes in Non-Coding RNAs

et al. 2021

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The non-coding RNAs (ncRNA) are RNA transcripts with different sizes, structures and biological functions that do not encode functional proteins. RNA G-quadruplexes (rG4s) have been found in small and long ncRNAs. The existence of an equilibrium between rG4 and stem−loop structures in ncRNAs and its effect on biological processes remains unexplored. For example, deviation from the stem−loop leads to deregulated mature miRNA levels, demonstrating that miRNA biogenesis can be modulated by ions or small molecules. In light of this, we report several examples of rG4s in certain types of ncRNAs, and the implications of G4 stabilization using small molecules, also known as G4 ligands, in the regulation of gene expression, miRNA biogenesis, and miRNA−mRNA interactions. Until now, different G4 ligands scaffolds were synthesized for these targets. The regulatory role of the above-mentioned rG4s in ncRNAs can be used as novel therapeutic approaches for adjusting miRNA levels.

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MicroRNA signatures associated with lymph node metastasis in intramucosal gastric cancer

Cited by 30 publications

References 53 publications

Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis

Hsa_circRNA_0045861 promotes renal injury in ureteropelvic junction obstruction via the microRNA-181d-5p/sirtuin 1 signaling axis

Novel Risk Associations between microRNA Polymorphisms and Gastric Cancer in a Chilean Population

Ligands as Stabilizers of G-Quadruplexes in Non-Coding RNAs

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