General Information of the Disease (ID: M6ADIS0010)
Name
Renal cell carcinoma
ICD
ICD-11: 2C90
Full List of Target Gene(s) of This m6A-centered Disease Response
ATP-binding cassette sub-family D member 1 (ABCD1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary knockdown of METTL3 in clear cell renal cell carcinoma cell line impaired both cell migration capacity and tumor spheroid formation in soft fibrin gel, a mechanical method for selecting stem-cell-like tumorigenic cells. METTL3 knockdown cells and functional studies confirmed that translation of ATP-binding cassette sub-family D member 1 (ABCD1).
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response ABC transporters hsa02010
Cell Process Cell migration and spheroid formation
In-vitro Model 786-O Renal cell carcinoma Homo sapiens CVCL_1051
A-498 Renal cell carcinoma Homo sapiens CVCL_1056
In-vivo Model A498 cells (1 × 106 cells) were resuspended in 100 uL of PBS and subcutaneously injected into the axillary fossa of nude mice (BALB/c-nude, 4 weeks old).
Aurora kinase B (AURKB)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary ALKBH5 plays a carcinogenic role in renal cell carcinoma by stabilizing Aurora kinase B (AURKB) mRNA in a m6A-dependent manner.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Pathway Response HIF-1 signaling pathway hsa04066
Cell Process Cell proliferation
Cell colony formation
Cell migration
Cell invasion
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model The nude mice were randomly grouped into 2 groups, of 5 mice each; 786-0 cells (7×106 in 100 L PBS) were stabilized with ALKBH5 knockdown lentiviral transfection vector (shALKBH5) or scramble vector (SCR) via subcutaneous injection into the left armpit of each mouse.
C-X-C motif chemokine 11 (CXCL11)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary RBM15 enhanced the stability of C-X-C motif chemokine 11 (CXCL11) mRNA in an m6A-dependent manner. These findings highlight the function of RBM15 in ccRCC and reveal a novel identified EP300/CBP-RBM15-CXCL11 signaling axis, which promotes ccRCC progression and provides new insight into ccRCC therapy.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator RNA-binding motif protein 15 (RBM15) WRITER
Target Regulation Up regulation
Pathway Response mRNA surveillance pathway hsa03015
RNA degradation hsa03018
Cell Process RNA stability
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model A total of 5 × 106 786O cells were subcutaneously injected into the left flanks of the mice.
Cyclin-dependent kinase 4 (CDK4)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary DMDRMR is a protumorigenic lncRNA that mediates the stabilization of IGF2BP3 targets in an m6A-dependent manner in clear cell renal cell carcinoma. IGF2BP3 and DMDRMR cooperate to play oncogenic roles. IGF2BP3 cooperates with DMDRMR to regulate Cyclin-dependent kinase 4 (CDK4) by enhancing mRNA stability.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Accelerating the G1-S transition
Cell invasion and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
In-vivo Model Stable DMDRMR knockdown (KD) and control cell lines were injected subcutaneously (s.c.; 1 × 107 cells/inoculum) into the flanks of recipient NOD/SCID/IL2Rγ-null (NSG) mice.
Cyclin-dependent kinase inhibitor 2A (CDKN2A)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [5]
Response Summary CircMET enhances mRNA decay of Cyclin-dependent kinase inhibitor 2A (CDKN2A) by direct interaction and recruitment of YTHDF2. CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Cell Process RNA stability
In-vitro Model UOK120 Papillary renal cell carcinoma Homo sapiens CVCL_B099
UOK109 Renal cell carcinoma Homo sapiens CVCL_B087
HK-2 [Human kidney] Normal Homo sapiens CVCL_0302
HEK293T Normal Homo sapiens CVCL_0063
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model The mice were subcutaneously inoculated with 786-O cells stably transfected with lentiviruses carrying sh-NC/sh-circMET, respectively (5 × 106, 200 uL).
Endothelial PAS domain-containing protein 1 (HIF-2Alpha/EPAS1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [6]
Response Summary MTHFD2 plays a critical role in controlling global N6-methyladenosine (m6A) methylation levels, including the m6A methylation of Endothelial PAS domain-containing protein 1 (HIF-2Alpha/EPAS1) mRNA, which results in enhanced translation of HIF-2-alpha. MTHFD2 links RNA methylation status to the metabolic state of tumor cells in Renal cell carcinoma.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Pathway Response Glycolysis / Gluconeogenesis hsa00010
Cell Process Aerobic glycolysis
In-vitro Model 786-O Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
RCC4 Clear cell renal cell carcinoma Homo sapiens CVCL_0498
In-vivo Model Xenograft tumors were generated by injection (5.0 × 106 cells/injection) of shMTHFD2 786-O and CAKI-1 lines and their respective shControl cell lines (n = 6 per line, sample size calculated for 80% power to detect a twofold difference with 95% confidence) subcutaneously into 6-week-old male Nu/J mice.
Epithelial splicing regulatory protein 2 (ESRP2)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary The expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. Lnc-LSG1 could be regulated by METTL14. Lnc-LSG1 can directly bind to Epithelial splicing regulatory protein 2 (ESRP2) protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Ubiquitination
In-vitro Model OS-RC-2 Clear cell renal cell carcinoma Homo sapiens CVCL_1626
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model For the xenograft tumor model, approximately 1 × 106 ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 106 ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 105 ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Integrin beta-4 (ITGB4)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [8]
Response Summary Knockdown of METTL14 promoted ccRCC cell migration, invasiveness and metastasis as well as stimulating the EMT process and the PI3K/AKT signal by overexpressing Integrin beta-4 (ITGB4).
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Cell Process Epithelial-mesenchymal transition
In-vitro Model OS-RC-2 Clear cell renal cell carcinoma Homo sapiens CVCL_1626
786-O Renal cell carcinoma Homo sapiens CVCL_1051
769-P Renal cell carcinoma Homo sapiens CVCL_1050
In-vivo Model Each group included 3 mice. 1.0?×?106 stably transfected ACHN cells in 150 uL were injected into a tail vein of each mouse, 45 days after which lungs were excised from the sacrificed mice and stained by Hematoxylin and Eosin (HE) Staining.
Mutated in multiple advanced cancers 1 (PTEN)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [9]
Response Summary Upregulation of METTL14 inhibited ccRCC cells proliferation and migration in vitro. Overexpression of METTL14 increased the m6A enrichment of Mutated in multiple advanced cancers 1 (PTEN), and promoted Pten expression. METTL14-enhanced Pten mRNA stability was dependent on YTHDF1.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [9]
Response Summary Upregulation of METTL14 inhibited ccRCC cells proliferation and migration in vitro. Overexpression of METTL14 increased the m6A enrichment of Mutated in multiple advanced cancers 1 (PTEN), and promoted Pten expression. METTL14-enhanced Pten mRNA stability was dependent on YTHDF1.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response PI3K-Akt signaling pathway hsa04151
Neutral amino acid transporter B(0) (SLC1A5)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [10]
Response Summary Genetic inactivation of FTO using multiple orthogonal approaches revealed that FTO inhibition selectively reduces the growth and survival of VHL-deficient cells in vitro and in vivo. Integrated analysis of transcriptome-wide m6A-seq and mRNA-seq analysis identified the glutamine transporter Neutral amino acid transporter B(0) (SLC1A5) as an FTO target that promotes metabolic reprogramming and survival of VHL-deficient ccRCC cells. GLS1 inhibitors that target mitochondrial glutaminase and the conversion of glutamine to glutamate are currently being evaluated in early-phase clinical trials in ccRCC. These findings identify FTO as a potential HIF-independent therapeutic target for the treatment of VHL-deficient renal cell carcinoma.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Responsed Drug GLS-IN-968 Investigative
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Central carbon metabolism in cancer hsa05230
HIF-1 signaling pathway hsa04066
Central carbon metabolism in cancer hsa05230
Metabolic pathways hsa01100
VEGF signaling pathway hsa04370
In-vitro Model UMRC2-vec (CCRCC isogenic cell lines that are VHL-deficient)
Nucleosome-remodeling factor subunit BPTF (BPTF)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [11]
Response Summary METTL14 deficiency promoted RCC metastasis in vitro and in vivo. Mechanistically, METTL14-mediated m6A modification negatively regulated the mRNA stability of Nucleosome-remodeling factor subunit BPTF (BPTF) and depended on BPTF to drive lung metastasis.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Pathway Response Glycerolipid metabolism hsa00561
Cell Process Glycolysis
In-vitro Model RenCa Mouse kidney carcinoma Mus musculus CVCL_2174
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model To generate a highly metastatic orthotopic xenograft model, 1 × 105 luciferase-expressing Renca cells (Luc-Renca) in 25 ul of 2:1 (v/v) PBS:Matrigel were injected into the right sub-renal capsule of the kidney of BALB/c mice (4 mice/group).
P2X purinoceptor 6 (P2RX6)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [12]
Response Summary In RCC, METTL14 implicated m6A modification in RCC and down-regulated P2X purinoceptor 6 (P2RX6) protein translation.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Cell Process Cell invasion and metastasis
In-vitro Model SW839 Clear cell renal cell carcinoma Homo sapiens CVCL_3604
SN12C-PM6 Renal cell carcinoma Homo sapiens CVCL_9549
OS-RC-2 Clear cell renal cell carcinoma Homo sapiens CVCL_1626
HEK293 Normal Homo sapiens CVCL_0045
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model For the in vivo metastasis assays, luciferase labeled OS-RC-2 cells stably expressing OE-P2RX6 or pWPI-vector were injected into the tail vein of 5 weeks old BALB/c nude mice (Sipper-BK laboratory animal Company, Shanghai, China).
PI3-kinase subunit alpha (PI3k/PIK3CA)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [13]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [14]
Response Summary FTO plays a critical anti-tumorigenic role in Clear Cell Renal Cell Carcinoma.Restored expression of FTO, through reducing m6A levels in mRNA transcripts of its critical target gene PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A), increases mitochondrial content, ROS production and oxidative damage, with the most important effect of repressed tumour growth.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Cell Process Oxidative stress
ROS production
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model Five- to 6-week-old male athymic nude mice purchased by Charles River were used for the xenograft model. 769-P cells stably expressing Ctrl, FTO and FTO-mut were trypsinized and washed twice to thrice with standardized PBS, and then, 5 × 106 cells in 100 uL of PBS was subcutaneously injected into the flanks of the mice (five mice per group). Mice were monitored twice every week for tumour growth, and tumour diameters were measured using a caliper.
RAC-alpha serine/threonine-protein kinase (AKT1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [13]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
Serine/threonine-protein kinase mTOR (MTOR)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [13]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/AKT/Serine/threonine-protein kinase mTOR (MTOR) markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-p70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
TNF receptor-associated factor 1 (TRAF1)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [15]
Response Summary In renal cell carcinoma, overexpression of TNF receptor-associated factor 1 (TRAF1) promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Responsed Drug Sunitinib Approved
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Cell Process RNA stability
Cell apoptosis
In-vitro Model OS-RC-2 Clear cell renal cell carcinoma Homo sapiens CVCL_1626
HUVEC-C Normal Homo sapiens CVCL_2959
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model For the xenograft tumor model, approximately 1 × 106 ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 106 ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 105 ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
Nuclear paraspeckle assembly transcript 1 (NEAT1)
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [16]
Response Summary In renal cell carcinoma, YTHDF2 accelerated the degradation of Nuclear paraspeckle assembly transcript 1 (NEAT1)_1 by selectively recognizing METTL14-mediated m6A marks on Nuclear paraspeckle assembly transcript 1 (NEAT1)_1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
Target Regulation Down regulation
Cell Process Cell proliferation and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Mouse subcutaneous xenograft and lung metastasis experiments were carried out with six 4-week-old male BALB/c nude mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [16]
Response Summary In renal cell carcinoma, YTHDF2 accelerated the degradation of Nuclear paraspeckle assembly transcript 1 (NEAT1)_1 by selectively recognizing METTL14-mediated m6A marks on Nuclear paraspeckle assembly transcript 1 (NEAT1)_1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Down regulation
Cell Process Cell proliferation and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Mouse subcutaneous xenograft and lung metastasis experiments were carried out with six 4-week-old male BALB/c nude mice.
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [4]
Response Summary DMDRMR is a protumorigenic lncRNA that mediates the stabilization of IGF2BP3 targets in an m6A-dependent manner in clear cell renal cell carcinoma. IGF2BP3 and DMDRMR cooperate to play oncogenic roles. IGF2BP3 cooperates with DMDRMR to regulate CDK4 by enhancing mRNA stability.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
Target Regulation Up regulation
Pathway Response Cell cycle hsa04110
Cell Process Accelerating the G1-S transition
Cell invasion and metastasis
In-vitro Model 769-P Renal cell carcinoma Homo sapiens CVCL_1050
786-O Renal cell carcinoma Homo sapiens CVCL_1051
ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
In-vivo Model Stable DMDRMR knockdown (KD) and control cell lines were injected subcutaneously (s.c.; 1 × 107 cells/inoculum) into the flanks of recipient NOD/SCID/IL2Rγ-null (NSG) mice.
Lnc_LSG1
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [7]
Response Summary The expression of METTL14 was negatively correlated to the prognosis, stage, and ccRCC tumor grade. Lnc-LSG1 could be regulated by METTL14. Lnc_LSG1 can directly bind to ESRP2 protein and promote ESRP2 degradation via facilitating ESRP2 ubiquitination.
Responsed Disease Renal cell carcinoma of kidney [ICD-11: 2C90.0]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response Ubiquitin mediated proteolysis hsa04120
Cell Process Ubiquitination
In-vitro Model OS-RC-2 Clear cell renal cell carcinoma Homo sapiens CVCL_1626
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
786-O Renal cell carcinoma Homo sapiens CVCL_1051
In-vivo Model For the xenograft tumor model, approximately 1 × 106 ccRCC cells suspended in 100 uL PBS were subcutaneously inoculated in the right flank of 5-week-old BALB/c nude mice. For the ccRCC orthotopic implantation model, approximately 1 × 106 ccRCC cells suspended in 30 uL Matrigel were injected under the renal capsule of 5-week-old BALB/c nude mice. After 6 weeks, the anesthetized mice were intraperitoneally injected with D-luciferin (Yeason) and imaged using an in vivo imaging system to detect tumor growth and metastasis. For the lung metastasis model, approximately 5 × 105 ccRCC cells suspended in PBS were injected into the tail vein of 5-week-old mice. After 6-8 weeks, mice were anesthetized and lung metastasis was imaged as above.
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [13]
Response Summary Knockdown of METTL3 could obviously promote cell proliferation, migration and invasion function, and induce G0/G1 arrest,METTL3 acts as a novel marker for tumorigenesis, development and survival of RCC. Knockdown of METTL3 promoted changes in pI3K/AKT/mTOR markers' expression with a gain in p-PI3k, p-AKT, p-mTOR and p-P70, and a loss of p-4EBP1.
Responsed Disease Renal cell carcinoma [ICD-11: 2C90]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Down regulation
Cell Process Epithelial-to-mesenchymal transition
Arrest cell cycle at G0/G1 phase
In-vitro Model ACHN Papillary renal cell carcinoma Homo sapiens CVCL_1067
Caki-1 Clear cell renal cell carcinoma Homo sapiens CVCL_0234
Caki-2 Papillary renal cell carcinoma Homo sapiens CVCL_0235
HK2 Normal Acipenser baerii CVCL_YE28
In-vivo Model Cells (5×106 cells in 200 uL) were suspended with 100 uL PBS and 100 uL Matrigel Matrix, and injected subcutaneously into the left armpit of each mouse.
References
Ref 1 The RNA N6-Methyladenosine Methyltransferase METTL3 Promotes the Progression of Kidney Cancer via N6-Methyladenosine-Dependent Translational Enhancement of ABCD1. Front Cell Dev Biol. 2021 Sep 23;9:737498. doi: 10.3389/fcell.2021.737498. eCollection 2021.
Ref 2 ALKBH5 promotes the proliferation of renal cell carcinoma by regulating AURKB expression in an m(6)A-dependent manner. Ann Transl Med. 2020 May;8(10):646. doi: 10.21037/atm-20-3079.
Ref 3 Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11. Free Radic Biol Med. 2022 May 1;184:135-147. doi: 10.1016/j.freeradbiomed.2022.03.031. Epub 2022 Apr 2.
Ref 4 DMDRMR-Mediated Regulation of m(6)A-Modified CDK4 by m(6)A Reader IGF2BP3 Drives ccRCC Progression. Cancer Res. 2021 Feb 15;81(4):923-934. doi: 10.1158/0008-5472.CAN-20-1619. Epub 2020 Dec 8.
Ref 5 CircMET promotes tumor proliferation by enhancing CDKN2A mRNA decay and upregulating SMAD3. Mol Cancer. 2022 Jan 18;21(1):23. doi: 10.1186/s12943-022-01497-w.
Ref 6 MTHFD2 links RNA methylation to metabolic reprogramming in renal cell carcinoma. Oncogene. 2019 Aug;38(34):6211-6225. doi: 10.1038/s41388-019-0869-4. Epub 2019 Jul 9.
Ref 7 METTL14-mediated Lnc-LSG1 m6A modification inhibits clear cell renal cell carcinoma metastasis via regulating ESRP2 ubiquitination. Mol Ther Nucleic Acids. 2021 Dec 17;27:547-561. doi: 10.1016/j.omtn.2021.12.024. eCollection 2022 Mar 8.
Ref 8 METTL14-mediated N(6)-methyladenosine modification of ITGB4 mRNA inhibits metastasis of clear cell renal cell carcinoma. Cell Commun Signal. 2022 Mar 19;20(1):36. doi: 10.1186/s12964-022-00831-5.
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