microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance

Monchusi, Bernice; Kaur, Mandeep

doi:10.18632/genesandcancer.202

Cited by 8 publications

(11 citation statements)

References 168 publications

(170 reference statements)

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“…The location of cg07504977 overlaps an active histone mark region within the promoter of LINC00263 [ 43 ], suggesting a role of methylation at this CpG site in the lncRNA transcription. Thus, it seems feasible that methylation at cg07504977 could affect LINC00263 expression, which in turn could directly adsorb or regulate the expression of miRNAs, and indirectly regulate the expression of miRNA target genes, e.g., miR-128, which directly inactivates ABCG1 [ 59 , 60 ]. Our results link methylation at cg07504977 to obesity and support this CpG as an emerging target for metabolic outcomes.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

et al. 2021

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Background The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.

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Section: Discussionmentioning

confidence: 99%

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

et al. 2021

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“…The MVA pathway is closely related to the occurrence and development of cancer [ 40 ]. Cholesterol-like metabolites produced by the MVA pathway can not only provide raw materials for the synthesis of the membranes of cancer cells but also regulate the function of glycosphingolipids on the surface of cancer cells to limit the immune recognition of tumors by the body [ 41 – 44 ]. The MVA signaling pathway regulates protein N-glycosylation associated with tumor metastasis [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

et al. 2023

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The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

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“…The MVA pathway is closely related to the occurrence and development of cancer 19 . Cholesterol-like metabolites produced by the MVA pathway can not only provide raw materials for the synthesis of the membranes of cancer cells but also regulate the function of glycosphingolipids on the surface of cancer cells to limit the immune recognition of tumors by the body 38,41,44,45 . The MVA signaling pathway regulates protein N-glycosylation associated with tumor metastasis 62 .…”

Section: Discussionmentioning

confidence: 99%

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

Wu¹,

Zheng²,

Zhou³

et al. 2022

Preprint

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The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is extremely low. microRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, the aim of this study was to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, as well as in human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that the inhibition of miR-122-5p expression led to the activation of p53, which in turn inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration as well as promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than that of their corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for the development of targeted drugs.

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microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance

Cited by 8 publications

References 168 publications

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer

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