m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00404)
Target Name Transcription factor SOX-2 (SOX2)
Gene Name SOX2
Chromosomal Location 3q26.33
Function
Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity).
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Gene ID 6657
Uniprot ID
SOX2_HUMAN
HGNC ID
HGNC:11195
Ensembl Gene ID
ENSG00000181449
KEGG ID
hsa:6657
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
SOX2 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line mouse embryonic stem cells Mus musculus
Treatment: METTL3-/- ESCs
Control: Wild type ESCs
 GSE145309
Regulation
logFC: 5.94E-01
p-value: 9.57E-57
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between SOX2 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 6.08E+00 GSE60213
In total 3 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. The exogenous overexpression of 3'UTR-less Transcription factor SOX-2 (SOX2) significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs.
Target Regulation Up regulation
Responsed Disease Glioblastoma ICD-11: 2A00.00
 Disease Info 
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process DNA repair
Nucleotide excision repair (hsa03420)
In-vitro Model Mouse immortalized astrocytes (A type of glial cell)
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell self-renewal
Stem cell frequency
Cell migration
In-vitro Model CCD-112CoN Normal Homo sapiens CVCL_6382
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
LS174T Colon adenocarcinoma Homo sapiens CVCL_1384
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Knockdown of METTL3 downregulated protein levels of Transcription factor SOX-2 (SOX2), CD133 and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [READER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by IGF2BP1
Cell Line A549 cell line Homo sapiens
Treatment: IGF2BP1 knockout A549 cells
Control: Wild type A549 cells
 GSE146546
Regulation
logFC: -2.55E+00
p-value: 6.23E-05
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary Dysregulation of IGF2BP1 by PADI2/MEK1/ERK signaling results in abnormal accumulation of oncogenic Transcription factor SOX-2 (SOX2) expression, therefore supporting the malignant state of EC.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
Cell Process RNA stability
In-vitro Model Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model Nude mice were subcutaneously injected with 1 × 107 PADI2 depleted or IGF2BP1 depleted Ishikawa cells on the left flanks, and the corresponding control cells on the right flanks.
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line human pluripotent stem cells Homo sapiens
Treatment: hILO ALKBH5knockout cells
Control: hILO wild type cells
 GSE163945
Regulation
logFC: -1.63E+00
p-value: 3.34E-04
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary HIF-dependent ALKBH5 expression increases in hypoxic TMEs, resulting in the demethylation of Transcription factor SOX-2 (SOX2) mRNA and the maintenance of the Endometrial cancer stem cells phenotype; these data indicate that ECSCs maintain their stemness by activating the HIF/ALKBH5/SOX2 axis under hypoxic conditions.
Target Regulation Up regulation
Responsed Disease Endometrial cancer ICD-11: 2C76
 Disease Info 
Pathway Response HIF-1 signaling pathway hsa04066
Signaling pathways regulating pluripotency of stem cells hsa04550
In-vitro Model EC cell line (Primary EC cells)
HEC-1-A Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
In-vivo Model A method of randomisation was used to determine the experimental groups. In total, 78 female BALB/c nu/nu mice (4-6-week-old) were selected at random and were divided into different groups. A total of 5 × 106 ISK cells or 1 × 104 ECSCisk were suspended in 100 uL of PBS and then were injected into the mice. After 2 weeks, the presence of tumours was examined. ISK cells (5 × 106, 5 × 105, 5 × 104, 1 × 104, or 1 × 103) and ECSCisk (1 × 104, 1 × 103, 1 × 102, 10, or 1) were injected and analysed for their abilities to form xenograft tumours. After 4 weeks, subsequent experiments were performed.
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Target Regulation Up regulation
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell self-renewal
Stem cell frequency
Cell migration
In-vitro Model CCD-112CoN Normal Homo sapiens CVCL_6382
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
LS174T Colon adenocarcinoma Homo sapiens CVCL_1384
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
Brain cancer [ICD-11: 2A00]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. The exogenous overexpression of 3'UTR-less Transcription factor SOX-2 (SOX2) significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs.
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process DNA repair
Nucleotide excision repair (hsa03420)
In-vitro Model Mouse immortalized astrocytes (A type of glial cell)
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell self-renewal
Stem cell frequency
Cell migration
In-vitro Model CCD-112CoN Normal Homo sapiens CVCL_6382
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
LS174T Colon adenocarcinoma Homo sapiens CVCL_1384
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3, acting as an oncogene, maintained Transcription factor SOX-2 (SOX2) expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in Colorectal carcinoma.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Signaling pathways regulating pluripotency of stem cells hsa04550
Cell Process Cell self-renewal
Stem cell frequency
Cell migration
In-vitro Model CCD-112CoN Normal Homo sapiens CVCL_6382
DLD-1 Colon adenocarcinoma Homo sapiens CVCL_0248
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HCT 15 Colon adenocarcinoma Homo sapiens CVCL_0292
HCT 8 Colon adenocarcinoma Homo sapiens CVCL_2478
LS174T Colon adenocarcinoma Homo sapiens CVCL_1384
RKO Colon carcinoma Homo sapiens CVCL_0504
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
SW620 Colon adenocarcinoma Homo sapiens CVCL_0547
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Knockdown of METTL3 downregulated protein levels of Transcription factor SOX-2 (SOX2), CD133 and CD44 in MCF-7 cells. METTL3 is upregulated in breast cancer, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
MCF-10A Normal Homo sapiens CVCL_0598
BT-474 Invasive breast carcinoma Homo sapiens CVCL_0179
Endometrial cancer [ICD-11: 2C76]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [4]
Response Summary Dysregulation of IGF2BP1 by PADI2/MEK1/ERK signaling results in abnormal accumulation of oncogenic Transcription factor SOX-2 (SOX2) expression, therefore supporting the malignant state of EC.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) READER
 Regulator Info 
Target Regulation Up regulation
Cell Process RNA stability
In-vitro Model Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
ECC-1 Endometrial Cancer Homo sapiens CVCL_7260
In-vivo Model Nude mice were subcutaneously injected with 1 × 107 PADI2 depleted or IGF2BP1 depleted Ishikawa cells on the left flanks, and the corresponding control cells on the right flanks.
Experiment 2 Reporting the m6A-centered Disease Response [5]
Response Summary HIF-dependent ALKBH5 expression increases in hypoxic TMEs, resulting in the demethylation of Transcription factor SOX-2 (SOX2) mRNA and the maintenance of the Endometrial cancer stem cells phenotype; these data indicate that ECSCs maintain their stemness by activating the HIF/ALKBH5/SOX2 axis under hypoxic conditions.
Responsed Disease Endometrial cancer [ICD-11: 2C76]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response HIF-1 signaling pathway hsa04066
Signaling pathways regulating pluripotency of stem cells hsa04550
In-vitro Model EC cell line (Primary EC cells)
HEC-1-A Endometrial adenocarcinoma Homo sapiens CVCL_0293
Ishikawa Endometrial adenocarcinoma Homo sapiens CVCL_2529
RL95-2 Endometrial adenosquamous carcinoma Homo sapiens CVCL_0505
In-vivo Model A method of randomisation was used to determine the experimental groups. In total, 78 female BALB/c nu/nu mice (4-6-week-old) were selected at random and were divided into different groups. A total of 5 × 106 ISK cells or 1 × 104 ECSCisk were suspended in 100 uL of PBS and then were injected into the mice. After 2 weeks, the presence of tumours was examined. ISK cells (5 × 106, 5 × 105, 5 × 104, 1 × 104, or 1 × 103) and ECSCisk (1 × 104, 1 × 103, 1 × 102, 10, or 1) were injected and analysed for their abilities to form xenograft tumours. After 4 weeks, subsequent experiments were performed.
References
Ref 1 Essential role of METTL3-mediated m(6)A modification in glioma stem-like cells maintenance and radioresistance. Oncogene. 2018 Jan 25;37(4):522-533. doi: 10.1038/onc.2017.351. Epub 2017 Oct 9.
Ref 2 METTL3 facilitates tumor progression via an m(6)A-IGF2BP2-dependent mechanism in colorectal carcinoma. Mol Cancer. 2019 Jun 24;18(1):112. doi: 10.1186/s12943-019-1038-7.
Ref 3 The m6A methyltransferase METTL3 promotes the stemness and malignant progression of breast cancer by mediating m6A modification on SOX2. J BUON. 2021 Mar-Apr;26(2):444-449.
Ref 4 PADI2-Catalyzed MEK1 Citrullination Activates ERK1/2 and Promotes IGF2BP1-Mediated SOX2 mRNA Stability in Endometrial Cancer. Adv Sci (Weinh). 2021 Jan 29;8(6):2002831. doi: 10.1002/advs.202002831. eCollection 2021 Mar.
Ref 5 Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA. Oncogenesis. 2020 Sep 11;9(9):81. doi: 10.1038/s41389-020-00265-z.