Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression

ABSTRACT: Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

SUBMITTER: Ding L

PROVIDER: S-EPMC8566597 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

PIWI-Interacting RNA Pathway Genes: Potential Biomarkers for Clear Cell Renal Cell Carcinoma.

Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system, yet effective diagnostic and prognostic markers are lacking. Recently, several of piRNA pathway genes have been reported to be associated with cancer diagnosis and prognosis, but their role in ccRCC is still unclear.MethodsWe analysed the expression of 27 piRNA pathway genes in 539 kidney renal clear cell carcinoma (KIRC) and 72 nontumor tissue samples (data from TCGA), and 12 mRNAs were significantly different. The aim was to sift the piRNA pathway genes that are correlated with ccRCC patient survival and to construct a piRNA pathway gene risk prognostic model using Kaplan-Meier survival curve and ROC curve, respectively.Results5 piRNA pathway genes (TDRD7, GPAT2, PLD6, SUV39H1, and DOM3Z) were picked out and used to construct the piRNA pathway gene risk model. Kaplan-Meier survival curve analysis showed that compared with that of the low-risk group of ccRCC patients, the OS of the high-risk group of ccRCC patients was significantly reduced. The predictive performance of the prognostic risk model was measured using a ROC curve, which individually showed AUC values for 1 year of 0.707, for 3 years of 0.713, and for 5 years of 0.701. Moreover, the mRNA and protein expression levels of TDRD7 were overexpressed in the ccRCC datasets (data from our cohort, TCGA, GEO, and CPTAC) and ccRCC cell lines, and the expression levels correlated with the clinicopathological characteristics in ccRCC. The Tumor Immune Estimation Resource (TIMER) showed that the mRNA expression level of TDRD7 was positively related to tumor immune infiltrating cells (TICs) in ccRCC. Mechanistically, gene set enrichment analysis (GSEA) was performed to uncover the mechanism of TDRD7 in ccRCC. In summary, the piRNA pathway genes,especially TDRD7, may be potential cancer diagnostic and prognostic biomarkers of ccRCC.

| S-EPMC8904100 | biostudies-literature

FBXL6 depletion restrains clear cell renal cell carcinoma progression.

Project description:BackgroundF-box proteins play important roles in cell cycle and tumorigenesis. However, its prognostic value and molecular function in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we established a survival model to evaluate the prognosis of patients with ccRCC using the F-box gene signature and investigated the function of FBXL6 in ccRCC.MethodsComprehensive bioinformatics analyses were used to identify differentially expressed F-box and hub genes associated with ccRCC carcinogenesis. Based on the F-box gene signature, we constructed a risk model and nomogram to predict the overall survival (OS) of patients with ccRCC and assist clinicians in decision-making. Finally, we verified the function and underlying molecular mechanisms of FBXL6 in ccRCC using CCK-8 and EdU assays, flow cytometry, and subcutaneous xenografts.ResultsA risk model based on FBXO39, FBXL6, FBXO1, and FBXL16 was developed. In addition, we drew a nomogram based on the risk score and clinical features to assess the prognosis of patients with ccRCC. Subsequently, we identified FBXL6 as an independent prognostic marker that was highly expressed in ccRCC cell lines. In vivo and in vitro assays revealed that the depletion of FBXL6 inhibited cell proliferation and induced apoptosis. We also demonstrated that SP1 regulated the expression of FBXL6.ConclusionsFBXL6 was first identified as a diagnostic and prognostic marker in patients with ccRCC. Loss of FBXL6 attenuates proliferation and induces apoptosis in ccRCC cells. SP1 was also found to regulate the expression of FBXL6.

| S-EPMC9526225 | biostudies-literature

MiR-223-3p promotes cell proliferation and metastasis by downregulating SLC4A4 in clear cell renal cell carcinoma.

Project description:MicroRNAs (miRNAs) are known to affect the occurrence and progression of cancer. We therefore evaluated the involvement of miR-223-3p in renal cell cancer. MiR-223-3p was highly expressed in clear cell renal cell cancer tissues. Clear cell renal cell cancer patients with higher miR-223-3p expression had higher tumor stages and grades and poorer prognoses. In renal cancer cells, overexpression of miR-223-3p enhanced cell proliferation and metastasis, while inhibition of miR-223-3p reduced the malignant capacity of the cells. MiR-223-3p was found to bind directly to solute carrier family 4, member 4 (SLC4A4) mRNA, thereby reducing SLC4A4 mRNA and protein expression. SLC4A4 overexpression restrained cell proliferation and metastasis by suppressing Kirsten rat sarcoma viral oncogene (KRAS) expression in renal cancer cells. SLC4A4 expression correlated negatively with miR-223-3p expression in patient samples. Given that miR-223-3p suppressed the SLC4A4/KRAS axis, miR-223-3p gene therapy could be an effective treatment for renal cancer.

| S-EPMC6366987 | biostudies-literature

PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma

Project description:Clear cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia PML protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation, and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity.

| S-SCDT-10_1038-S44321-024-00077-3 | biostudies-other

Piwi-Interacting RNAs (piRNAs) Are Dysregulated in Renal Cell Carcinoma and Associated with Tumor Metastasis and Cancer-Specific Survival.

Project description:Piwi-interacting RNAs (piRNAs) are a distinct group of small noncoding RNAs (sncRNAs) that silence transposable genetic elements to protect genome integrity. Because of their limited expression in gonads and sequence diversity, piRNAs remain the most mysterious class of small RNAs. Studies have shown piRNAs are present in somatic cells and dysregulated in gastric, breast and liver cancers. By deep sequencing 24 frozen benign kidney and clear cell renal cell carcinoma (ccRCC) specimens and using the publically available piRNA database, we found 26,991 piRNAs present in human kidney tissue. Among 920 piRNAs that had at least two copies in one specimen, 19 were differentially expressed in benign kidney and ccRCC tissues, and 46 were associated with metastasis. Among the metastasis-related piRNAs, we found three piRNAs (piR-32051, piR-39894 and piR-43607) to be derived from the same piRNA cluster at chromosome 17. We confirmed the three selected piRNAs not to be miRNAs or miRNA-like sncRNAs. We further validated the aberrant expression of the three piRNAs in a 68-case formalin-fixed and paraffin-embedded (FFPE) ccRCC tissue cohort and showed the up-regulation of the three piRNAs to be highly associated with ccRCC metastasis, late clinical stage and poor cancer-specific survival.

| S-EPMC4534471 | biostudies-literature

The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma.

Project description:PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1. Our study reports a physiological preclinical ccRCC mouse model that recapitulates somatic mutations in human ccRCC and provides mechanistic and therapeutic insights into PBRM1 mutated subtypes of human ccRCC.

| S-EPMC5431084 | biostudies-literature

Identification of metastasis associated genes in clear cell renal cell carcinoma

Project description: Not available

| S-DIXA-D-1153 | biostudies-other

piwi-interacting RNA sequencing of 2 paired clear cell renal cell carcinoma tissues and adjacent normal tissues

Project description:Clear cell renal cell carcinoma is one of the most common diagnostic tumor, with nearly one third patients diagnosed as metastatic ccRCC. Although increasing number of studies have revealed that piwi-interacting RNAs were aberrantly expressed in diverse type of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particular in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC was selected by using piRNA-sequencing combined with analyzing TCGA data, from which piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further studies revealed that piR-57125 modulated ccRCC metastasis through AKT/ERK pathway. Those data indicate that piR-57125 restrains ccRCC metastasis through directly targeting CCL3 and inhibiting AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

2021-09-08 | GSE183496 | GEO

RBM47 restrains renal cell carcinoma progression and chemoresistance through interacting with lncRNA HOXB-AS1.

Project description:RNA binding proteins have the critical role in renal cell carcinoma (RCC) progression. However, the role of RBM47 in RCC has not been elucidated. In this study, we found that RBM47 was downregulated in RCC tissues and its expression was negatively correlated with the prognosis of RCC patients. Also, we found that the expression of RBM47 was regulated by CBP/P300-mediated H3K27ac in RCC. Functionally, RBM47 restrained RCC cells proliferation and metastasis. Mechanistically, RBM47 interfered with the interaction between HOXB-AS1 and p53 proteins via directly binding with HOXB-AS1, finally promoted the entry of p53 into the nucleus and therefore activated the p53 signaling. Moreover, RBM47 had a synergistic anticancer effect with sunitinib both in vivo and in vitro.

| S-EPMC10475063 | biostudies-literature

IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma.

Project description:Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.

| S-EPMC7230261 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data