m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0032)
Name
Sorafenib
Synonyms
Nexavar; Sorafenibum; Sorafenib [INN]; Nexavar (TN); Sorafenib (INN); N-[4-Chloro-3-(trifluoromethyl)phenyl]-N'-[4-[2-(N-methylcarbamoyl)-4-pyridyloxy]phenyl]urea; N-(4-Chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea; N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-methylcar bamoyl)-4-pyridyloxy)phenyl)urea; 4(4-{3-[4-Chloro-3-(trifluoromethyl)phenyl]ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide; 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate; 4-(4-{3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido}phenoxy)-N(sup 2)-methylpyridine-2-carboxamide; 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methyl-pyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl]amino]phenoxy]-N-methyl-2-pyridinecarboxamide; 4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE; Sorafenib (Pan-TK inhibitor)
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Status Approved [1]
Structure
Formula
C21H16ClF3N4O3
InChI
InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)
InChIKey
MLDQJTXFUGDVEO-UHFFFAOYSA-N
PubChem CID
216239
TTD Drug ID
D0W5HK
DrugBank ID
DB00398
Full List of m6A Targets Related to This Drug
Autophagy protein 5 (ATG5)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, Autophagy protein 5 (ATG5), ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, Autophagy protein 5 (ATG5), ATG7, ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Autophagy-related protein 16-1 (ATG16L1)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and Autophagy-related protein 16-1 (ATG16L1).
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Beclin-1 (BECN1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [3]
Response Summary Analyzed the effect of sorafenib on HSC ferroptosis and m6A modification in advanced fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. YTHDF1 promotes Beclin-1 (BECN1) mRNA stability and autophagy activation via recognizing the m6A binding site within BECN1 coding regions.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Ferroptosis
Cell autophagy
In-vitro Model HSC (Hematopoietic stem cell)
In-vivo Model VA-Lip-Mettl4-shRNA, VA-Lip-Fto-Plasmid and VA-Lip-Ythdf1-shRNA (0.75 mg/kg) were injected intravenously 3 times a week.
Forkhead box protein O3 (FOXO3)
 Target Info 
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [4]
Response Summary METTL3 and Forkhead box protein O3 (FOXO3) levels are tightly correlated in hepatocellular carcinoma patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
Pathway Response FoxO signaling pathway hsa04068
Cell Process Cell Transport
Cell catabolism
Cell autophagy
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
Hepa 1-6 Hepatocellular carcinoma of the mouse Mus musculus CVCL_0327
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HUVEC-C Normal Homo sapiens CVCL_2959
WRL 68 Endocervical adenocarcinoma Homo sapiens CVCL_0581
In-vivo Model For the drug-resistant subcutaneous tumor models, drug administration was adopted when the tumors reached about 50 mm3 in size, at which point mice were randomized for treatment with DMSO(intraperitoneally) or sorafenib (50 mg/kg/every 2 days, intraperitoneally). For the patient-derived tumor xenograft model, drug administration began 4 weeks after tumors reached about 100 mm3 in size with sorafenib (50 mg/kg/every 3 days, intraperitoneally) or siCtrl/siMETTL3 intratumor injection.
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Cell Process Cell autophagy
Experiment 3 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising Forkhead box protein O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Cell Process Cell autophagy
Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [5]
Response Summary The Hepatocyte nuclear factor 3-gamma (HNF3gamma/FOXA3) reduction in hepatocellular carcinoma could be mediated by METTL14-dependent m6A methylation of HNF3-Gamma mRNA. HNF3-Gamma plays an essential role in HCC differentiation and serves as a therapeutic target and predictor of sorafenib benefit in patients.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
 Regulator Info 
Target Regulation Down regulation
Cell Process Membrane transport
Cell apoptosis
In-vitro Model HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
In-vivo Model When xenografted tumor growth reached 500 mm3, the mice were subjected to intratumoral injection of Ad-con or Ad-HNF3γ every other day. For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm3 and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days.
Translocating chain-associated membrane protein 2 (TRAM2)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [6]
Response Summary Overexpression of RBM15B promotes HCC cell proliferation and invasion and induces sorafenib resistance in HCC cells. RBM15B is transcriptionally activated by YY1 and regulates the stability of Translocating chain-associated membrane protein 2 (TRAM2) mRNA in an m6A-dependent manner.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator RNA-binding motif protein 15B (RBM15B) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model SK-HEP-1 Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
L-02 Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2.215 (Hep-G2.215 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences)
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
HCCLM3 Adult hepatocellular carcinoma Homo sapiens CVCL_6832
7721 (Human hepatic malignant cell line)
In-vivo Model HCC-LM3 cells transfected with sh-NC and sh-RBM15B-3 were injected into the axilla or tail vein of mice.
Ubiquitin-like modifier-activating enzyme ATG7 (ATG7)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, Ubiquitin-like modifier-activating enzyme ATG7 (ATG7), ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Ubiquitin-like protein ATG12 (ATG12)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including ATG3, ATG5, ATG7, Ubiquitin-like protein ATG12 (ATG12), and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Ubiquitin-like-conjugating enzyme ATG3 (ATG3)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary METTL3 can sensitise hepatocellular carcinoma cells to sorafenib through stabilising forkhead box class O3 (FOXO3) in an m6A-dependent manner and translated by YTHDF1, thereby inhibiting the transcription of autophagy-related genes, including Ubiquitin-like-conjugating enzyme ATG3 (ATG3), ATG5, ATG7, ATG12, and ATG16L1.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response FoxO signaling pathway hsa04068
Autophagy hsa04140
Cell Process Cell autophagy
Long intergenic non-protein coding RNA 1273 (LINC01273)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [7]
Response Summary Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [7]
Response Summary Long intergenic non-protein coding RNA 1273 (LINC01273) was modified with m6A, METTL3 increased LINC01273 m6A modification, followed by LINC01273 decay in the presence of YTHDF2, a m6A 'reader'. And LINC01273 plays a key role in sorafenib resistant HCC cells.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
In-vitro Model SMMC-7721 Endocervical adenocarcinoma Homo sapiens CVCL_0534
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
NIFK antisense RNA 1 (NIFK-AS1)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [8]
Response Summary Identified the lncRNA NIFK antisense RNA 1 (NIFK-AS1) as being highly expressed in hepatocellular carcinoma tissues and cells, promotes disease progression and sorafenib resistance, and showed this up-regulation resulted from METTL3-dependent m6A methylation.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
In-vitro Model Hep 3B2.1-7 Childhood hepatocellular carcinoma Homo sapiens CVCL_0326
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
Huh-7 Adult hepatocellular carcinoma Homo sapiens CVCL_0336
MHCC97-H Adult hepatocellular carcinoma Homo sapiens CVCL_4972
THLE-3 Normal Homo sapiens CVCL_3804
In-vivo Model For the PDX model, fresh patient HCC tissues were cut into fragments with a volume of 3 × 3 mm3 and then implanted subcutaneously into the flanks of nude mice. The mice were given sorafenib (30 mg/kg) or vehicle orally twice a week for 24 days. This procedure was approved by the Ethics Committee of Jinling Hospital.
hsa_circ_0087293 (SORE)
 Target Info 
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [9]
Response Summary N6-methyladenosine-modified hsa_circ_0087293 (SORE) sequestered miR-103a-2-5p and miR-660-3p by acting as a microRNA sponge, thereby competitively activating the Wnt/beta-catenin pathway and inducing sorafenib resistance in hepatocellular carcinoma.
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12.02
 Disease Info 
Cell Process Cell apoptosis
In-vitro Model HCC sorafenib-resistant (SR) cell line HepG2-SR (Sorafenib-resistant HepG2 cell line)
HCC sorafenib-resistant (SR) cell line Huh7-SR (Sorafenib-resistant Huh7 cell line)
HCC sorafenib-resistant (SR) cell line LM3-SR (Sorafenib-resistant LM3 cell line)
HCC sorafenib-resistant (SR) cell line SKhep1-SR (Sorafenib-resistant SKhep1 cell line)
In-vivo Model The first CDX generation was constructed in 4-6 week-old male BALB/c nude mice and treated with sorafenib (30 mg/kg daily, oral gavage). Twelve weeks later, the most resistant xenograft was disaggregated and implanted subcutaneously into 4-6 week-old BALB/c nude mice as the second SR-CDX. Four weeks after implantation, the second SR-CDX mice were treated with sorafenib (30 mg/kg daily, oral gavage) and locally injected with sh-circRNA-SORE lentivirus or its negative control (twice a week for 2 weeks).
References
Ref 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5711).
Ref 2 RNA N6-methyladenosine: a new player in autophagy-mediated anti-cancer drug resistance. Br J Cancer. 2021 May;124(10):1621-1622. doi: 10.1038/s41416-021-01314-z. Epub 2021 Mar 15.
Ref 3 N(6)-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells. Redox Biol. 2021 Nov;47:102151. doi: 10.1016/j.redox.2021.102151. Epub 2021 Sep 26.
Ref 4 RNA m(6) A methylation regulates sorafenib resistance in liver cancer through FOXO3-mediated autophagy. EMBO J. 2020 Jun 17;39(12):e103181. doi: 10.15252/embj.2019103181. Epub 2020 May 5.
Ref 5 m6A RNA methylation-mediated HNF3Gamma reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance. Signal Transduct Target Ther. 2020 Dec 26;5(1):296. doi: 10.1038/s41392-020-00299-0.
Ref 6 YY1-Targeted RBM15B Promotes Hepatocellular Carcinoma Cell Proliferation and Sorafenib Resistance by Promoting TRAM2 Expression in an m6A-Dependent Manner. Front Oncol. 2022 Apr 14;12:873020. doi: 10.3389/fonc.2022.873020. eCollection 2022.
Ref 7 Long intergenic non-protein coding RNA 1273 confers sorafenib resistance in hepatocellular carcinoma via regulation of methyltransferase 3. Bioengineered. 2022 Feb;13(2):3108-3121. doi: 10.1080/21655979.2022.2025701.
Ref 8 Upregulation of lncRNA NIFK-AS1 in hepatocellular carcinoma by m(6)A methylation promotes disease progression and sorafenib resistance. Hum Cell. 2021 Nov;34(6):1800-1811. doi: 10.1007/s13577-021-00587-z. Epub 2021 Aug 10.
Ref 9 N(6)-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating Beta-catenin signaling. Mol Cancer. 2020 Nov 23;19(1):163. doi: 10.1186/s12943-020-01281-8.