29 m⁶A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset Analyses

Table 5

The reactive oxygen species (ROS) regulators were the targets of RNA methylation regulators in human cell studies. TREW (Target of m⁶A Readers, Erasers, and Writers) was downloaded from Met-DB v2.0 (MeT-DB V2.0: the Methyl Transcriptome DataBase Version 2.0 http://180.208.58.19/metdb_v2/html/index.php PMID: 29126312). 165 ROS regulators were examined, and the result showed 18 ROS regulators (F2RL1, PDK4, TIGAR, BCL2, SESN2, GNAI2, DDIT4, SH3PXD2A, FOXM1, AATF, TGFB1, TSPO, G6PD, GNAI3, and CYP1B1) were modulated by writers KIAA1429, METTL14, METTL3, and WTAP (several ROS regulators were modulated in more than one position in the chromosome or by more than one RNA methylation regulator). The deficiencies of writers (KIAA1429, METTL14, METTL3, and WTAP) can downregulate the m6A modification of ROS regulators ().

Targeted-ROS regulator	Type	m6A methyl-regulator	adj	p_treated	p_control	Log2_OR	Log2_RR		Experiment (modification-RNA methylation regulators-cell)	PMID
F2RL1	Writer	KIAA1429	0.01	0.35	0.59	-1.39	-0.74	893.65	m6A-KIAA1429-si-A549	24981863
F2RL1	Writer	KIAA1429	0.02	0.46	0.75	-1.86	-0.72	1959.11	m6A-KIAA1429-si-A549	24981863
PDK4	Writer	KIAA1429	0.02	0.11	0.69	-4.12	-2.60	91.22	m6A-KIAA1429-si-A549	24981863
TIGAR	Writer	KIAA1429	0.04	0.19	0.73	-3.56	-1.95	309.32	m6A-KIAA1429-si-A549	24981863
BCL2	Writer	METTL14	0.03	0.63	0.95	-3.37	-0.58	130.91	m6A-METTL14-sh2-A549	24981863
SESN2	Writer	METTL3	0.03	0.25	0.46	-1.35	-0.88	80.55	m6A-METTL3-kd-Hela	24316715
GNAI2	Writer	METTL3	≤0.01	0.26	0.41	-0.99	-0.66	474.67	m6A-METTL3-kd-Hela	24316715
GNAI2	Writer	METTL3	≤0.01	0.26	0.41	-0.99	-0.66	474.67	m6A-METTL3-kd-Hela	24316715
DDIT4	Writer	METTL3	≤0.01	0.27	0.44	-1.05	-0.68	1549.26	m6A-METTL3-kd-Hela	24316715
DDIT4	Writer	METTL3	≤0.01	0.27	0.44	-1.05	-0.68	1549.26	m6A-METTL3-kd-Hela	24316715
DDIT4	Writer	METTL3	≤0.01	0.27	0.44	-1.05	-0.68	1549.26	m6A-METTL3-kd-Hela	24316715
SH3PXD2A	Writer	METTL3	0.03	0.55	0.60	-0.29	-0.13	2889.11	m6A-METTL3-kd-Hela	24316715
SH3PXD2A	Writer	METTL3	0.03	0.55	0.60	-0.29	-0.13	2889.11	m6A-METTL3-kd-Hela	24316715
SH3PXD2A	Writer	METTL3	0.03	0.55	0.60	-0.29	-0.13	2889.11	m6A-METTL3-kd-Hela	24316715
SH3PXD2A	Writer	METTL3	0.03	0.55	0.60	-0.29	-0.13	2889.11	m6A-METTL3-kd-Hela	24316715
FOXM1	Writer	METTL3	0.02	0.33	0.40	-0.43	-0.27	427.19	m6A-METTL3-kd-Hela	24316715
AATF	Writer	METTL3	≤0.01	0.19	0.39	-1.40	-1.00	132.56	m6A-METTL3-kd-Hela	24316715
TGFB1	Writer	METTL3	≤0.01	0.46	0.60	-0.79	-0.37	1205.15	m6A-METTL3-kd-Hela	24316715
TSPO	Writer	METTL3	0.01	0.25	0.37	-0.78	-0.54	186.38	m6A-METTL3-kd-Hela	24316715
G6PD	Writer	METTL3	≤0.01	0.36	0.40	-0.28	-0.17	2992.01	m6A-METTL3-kd-Hela	24316715
GNAI3	Writer	WTAP	0.02	0.17	0.46	-2.01	-1.41	154.65	m6A-WTAP-kd-Hela	24316715
GNAI3	Writer	WTAP	0.02	0.17	0.46	-2.01	-1.41	154.65	m6A-WTAP-kd-Hela	24316715
TIGAR	Writer	WTAP	0.01	0.19	0.56	-2.42	-1.54	104.56	m6A-WTAP-kd-Hela	24316715
CYP1B1	Writer	WTAP	0.02	0.50	0.95	-4.33	-0.93	583.55	m6A-WTAP-si-A549	24981863
DDIT4	Writer	WTAP	≤0.01	0.46	0.73	-1.66	-0.66	825.45	m6A-WTAP-si-Hek293T	24981863

Met-DB v2.0 contains a significant increase in context-specific m⁶A peaks and single-base sites predicted from 185 samples from 26 separate studies for 7 species. It has also been updated to include a new database for targets of m⁶A readers, erasers, and writers, as well as additional functional data gathering. The abbreviation TREW stands for Target of m⁶A Readers, Erasers, and Writers. To discover their target sits, we collected ParCLIP-seq and MeRIP-seq data for 8 regulator/reader proteins (including FTO, KIAA1429, METTL14, METTL3, WTAP, HNRNPC, YTHDC1, and YTHDF1) from 10 independent studies. Then, the differential m6A peaks that showed significant hypermethylation (hypomethylation) after knocking down of a demethylase (methylase) were determined to the target peaks. p_treat: peak of treated group; p_control: peak of control group; OR: odds ratio; RR: relative risk or risk ratio.