Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10341)
Regulator Name 3'-5' RNA helicase YTHDC2
Synonyms
YTH domain-containing protein 2
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Gene ID 64848
Regulator Type Protein coding
Uniprot ID Q9H6S0
Sequence
MSRPSSVSPRQPAPGGGGGGGPSPCGPGGGGRAKGLKDIRIDEEVKIAVNIALERFRYGD
QREMEFPSSLTSTERAFIHRLSQSLGLVSKSKGKGANRYLTVKKKDGSETAHAMMTCNLT
HNTKHAVRSLIQRFPVTNKERTELLPKTERGNVFAVEAENREMSKTSGRLNNGIPQIPVK
RGESEFDSFRQSLPVFEKQEEIVKIIKENKVVLIVGETGSGKTTQIPQFLLDDCFKNGIP
CRIFCTQPRRLAAIAVAERVAAERRERIGQTIGYQIRLESRVSPKTLLTFCTNGVLLRTL
MAGDSTLSTVTHVIVDEVHERDRFSDFLLTKLRDLLQKHPTLKLILSSAALDVNLFIRYF
GSCPVIYIQGRPFEVKEMFLEDILRTTGYTNKEMLKYKKEKQQEEKQQTTLTEWYSAQEN
SFKPESQRQRTVLNVTDEYDLLDDGGDAVFSQLTEKDVNCLEPWLIKEMDACLSDIWLHK
DIDAFAQVFHLILTENVSVDYRHSETSATALMVAAGRGFASQVEQLISMGANVHSKASNG
WMALDWAKHFGQTEIVDLLESYSATLEFGNLDESSLVQTNGSDLSAEDRELLKAYHHSFD
DEKVDLDLIMHLLYNICHSCDAGAVLIFLPGYDEIVGLRDRILFDDKRFADSTHRYQVFM
LHSNMQTSDQKKVLKNPPAGVRKIILSTNIAETSITVNDVVFVIDSGKVKEKSFDALNFV
TMLKMVWISKASAIQRKGRAGRCRPGICFRLFSRLRFQNMLEFQTPELLRMPLQELCLHT
KLLAPVNCPIADFLMKAPEPPPALIVRNAVQMLKTIDAMDTWEDLTELGYHLADLPVEPH
LGKMVLCAVVLKCLDPILTIACTLAYRDPFVLPTQASQKRAAMLCRKRFTAGAFSDHMAL
LRAFQAWQKARSDGWERAFCEKNFLSQATMEIIIGMRTQLLGQLRASGFVRARGGGDIRD
VNTNSENWAVVKAALVAGMYPNLVHVDRENLVLTGPKEKKVRFHPASVLSQPQYKKIPPA
NGQAAAIKALPTDWLIYDEMTRAHRIANIRCCSAVTPVTILVFCGPARLASNALQEPSSF
RVDGIPNDSSDSEMEDKTTANLAALKLDEWLHFTLEPEAASLLLQLRQKWHSLFLRRMRA
PSKPWSQVDEATIRAIIAVLSTEEQSAGLQQPSGIGQRPRPMSSEELPLASSWRSNNSRK
SSADTEFSDECTTAERVLMKSPSPALHPPQKYKDRGILHPKRGTEDRSDQSSLKSTDSSS
YPSPCASPSPPSSGKGSKSPSPRPNMPVRYFIMKSSNLRNLEISQQKGIWSTTPSNERKL
NRAFWESSIVYLVFSVQGSGHFQGFSRMSSEIGREKSQDWGSAGLGGVFKVEWIRKESLP
FQFAHHLLNPWNDNKKVQISRDGQELEPLVGEQLLQLWERLPLGEKNTTD

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Family DEAD box helicase family
Function
3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells. Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability. Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs. Acts by binding and promoting degradation of m6A- containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease. Required for both spermatogenesis and oogenesis.

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HGNC ID
HGNC:24721
KEGG ID hsa:64848
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
3'-5' RNA helicase YTHDC2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
BEAS-2B cells Normal Homo sapiens CVCL_0168
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H441 cells Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H1650 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation.

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Response regulation The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.
4F2 cell-surface antigen heavy chain (SLC3A2) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
BEAS-2B cells Normal Homo sapiens CVCL_0168
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H441 cells Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H1650 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation.

    Click to Show/Hide
Response regulation The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 3'-5' RNA helicase YTHDC2 Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
BEAS-2B cells Normal Homo sapiens CVCL_0168
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H441 cells Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H1650 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation.

    Click to Show/Hide
Response regulation The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 3'-5' RNA helicase YTHDC2 Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
BEAS-2B cells Normal Homo sapiens CVCL_0168
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
NCI-H441 cells Lung papillary adenocarcinoma Homo sapiens CVCL_1561
NCI-H1650 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1483
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
In Vivo Model
For xenograft experiments, 1.5 x 107 Doxocycline (Dox)-inducible YTHDC2-expressing H1299 cells were subcutaneously injected into 4-6-week-oldathymic nude mice. At day 14 post inoculation, mice were randomly divided into 2 groups for further administrating with or without Dox (30 mg/kg) every other day. Tumors were assessed after sacrificing the mice at day 28 after implantation.

    Click to Show/Hide
Response regulation The m6A reader YT521-B homology containing 2 (YTHDC2) has been identified to inhibit lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. YTHDC2 also suppresses SLC3A2 subunit via inhibiting HOXA13-mediated SLC3A2 transcription.
References
Ref 1 Targeting SLC3A2 subunit of system X(C)(-) is essential for m(6)A reader YTHDC2 to be an endogenous ferroptosis inducer in lung adenocarcinoma. Free Radic Biol Med. 2021 May 20;168:25-43. doi: 10.1016/j.freeradbiomed.2021.03.023. Epub 2021 Mar 27.