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MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [bulkRNA-seq]

ABSTRACT: MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [bulkRNA-seq]

PROVIDER: PRJNA885780 | ENA |

REPOSITORIES: ENA

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MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [bulkRNA-seq]

Project description:The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874–mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874–induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.

2022-10-03 | GSE214507 | GEO

MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [scRNA-seq]

2022-10-03 | GSE214508 | GEO

MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway

Project description:MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway

| PRJNA885778 | ENA

MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [scRNA-seq]

Project description:MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway [scRNA-seq]

| PRJNA885781 | ENA

MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway.

Project description:The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been elucidated. We identified phosphomevalonate kinase (PMVK), a key mevalonate pathway enzyme, and sterol regulatory element-binding factor 2 (SREBF2), the master cholesterol biosynthesis regulator, as direct miR‑874 targets. Next-generation sequencing analysis revealed a significant miR-874-mediated downregulation of PMVK and SREBF2 gene expression and p53 pathway enrichment. Luciferase reporter assays showed that miR-874 directly regulated PMVK and SREBF2. miR-874-induced apoptosis was p53 dependent, and single-cell RNA sequencing analysis demonstrated that miR-874 transfection resulted in apoptosis and p53 pathway activation. Downregulation of PMVK expression also caused cell cycle arrest and p53 pathway activation, which was rescued by geranylgeranyl pyrophosphate (GGPP) supplementation. Analysis of The Cancer Genome Atlas (TCGA) database indicated a negative correlation between miR-874 and PMVK expression and between miR-874 and SREBF2 expression. These findings suggest that miR-874 suppresses the mevalonate pathway by targeting SREBF2 and PMVK, resulting in GGPP depletion, which activates the p53 pathway and promotes cycle arrest or apoptosis.

| S-EPMC9630378 | biostudies-literature

MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-03 | GSE214509 | GEO

Pharmacological targeting Netrin-1 inhibits EMT in cancer [BulkRNA-seq]

Project description:Pharmacological targeting Netrin-1 inhibits EMT in cancer [BulkRNA-seq]

| PRJNA980661 | ENA

p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression

Project description:We have discovered that loss of wild-type p53 correlates with elevated expression of mevalonate pathway genes in murine liver cancer and in human tumors. Mechanistically p53 blocks activation of SREBP-2, the master transcriptional regulator of this pathway, by transcriptionally inducing the ABCA1 cholesterol transporter gene, which inhibits SREBP-2 maturation. In mice the increase in mevalonate gene expression occurs in premalignant p53-null hepatocytes at a stage when p53 is needed to actively suppress tumorigenesis. Either RNAi mediated suppression of key genes in the mevalonate pathway or pharmacological inhibition of its rate-limiting enzyme restricts the development of mouse hepatocellular carcinomas driven by p53 loss. Conversely, like p53 loss, ablation of ABCA1 promotes tumorigenesis in a murine model and is associated with increased SREBP-2 maturation. Our findings thereby demonstrate that repression of the mevalonate pathway is a crucial component of p53-mediated tumor suppression and outline the mechanism by which this occurs.

2018-10-23 | GSE121558 | GEO

Populus trichocarpa strain:Besc-874

Project description:Populus trichocarpa strain:Besc-874 Genome sequencing

| PRJNA249999 | ENA

Mevalonate pathway inhibition affects bladder cancer metastasis

Project description:Metastasis is an important factor affecting the prognosis and survival of bladder cancer (BLCA) patients. Our previous study found that the mevalonate pathway is associated with the migratory ability of BLCA cells, but the exact mechanism is unclear. Here, we found that BLCA patients with mevalonate pathway activation had a poorer prognosis. Inhibition of the mevalonate pathway (FDPS knockdown, simvastatin or zoledronic acid) significantly reduced the migratory ability of BLCA cells. Therefore, we tested the changes of key genes after knocking down the key enzymes of the mevalonate pathway, FDPS and SQLE1, and the transcription factor YY1 in bladder cancer cells using RNA sequencing.

2024-09-08 | GSE252007 | GEO

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