m6A-centered Disease Response Information
General Information of the Disease (ID: M6ADIS0010)
Name |
Renal cell carcinoma
|
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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. | |||
DMDRMR
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. | |||
p-P70
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