Progress and application of epitranscriptomic m⁶A modification in gastric cancer

Figures & data

Table 1. Changes in total RNA m⁶A in GC.

Samples	Quantitative method	Change in m^6A ^a	References
12 pairs of cancerous and adjacent tissues	colorimetry	elevated	Sun et al
5 pairs of cancerous and adjacent tissues	LC-MS/MS	elevated	Yue et al
17 pairs of cancerous and adjacent tissues	colorimetry	elevated	Liu et al
5 pairs of cancerous and adjacent tissues	colorimetry	elevated	Hu et al
40 pairs of cancerous and adjacent tissues	colorimetry	elevated	Zhou et al

a Levels in GC tissues compared to those in adjacent tissues

Figure 1. m⁶A regulators in GC cell

Different m⁶A regulators have been confirmed to get involved in the process and molecular functions of RNA m⁶A modification in GC. Writers (including METTL3, METTL14, WTAP, RBM15, et al) and erasers (including FTO, ALKBH1, ALKBH5) make RNA m⁶A modification a dynamic and reversible process in GC cells. And readers are responsible for different downstream effects of m⁶A in GC cells, such as (a) HuR, IGF2BP1, IGF2BP2 and IGF2BP3 in the nucleus facilitate the proliferation, metastasis, or EMT program of GC cells by promoting target mRNA stability; (b) DGCR8 facilitates processing of m⁶A modified pri-miR-17-92, which promotes the proliferation of GC cells; (c) The deficiency of YTHDF1, which regulates FZD7 and USP14 translation, inhibits the proliferation and metastasis of GC cells; (d) YTHDF2 in the cytoplasm enhances GC cell proliferation, migration and invasion by promoting PTEN mRNA decay.

Table 2. m⁶A-modified mRNAs in GC.

mRNA	m^6A Regulator		Function of Regulators	Pathway	Role of target	Reference
PKMYT1	ALKBH5 IGF2BP3	Eraser Reader	Demethylating m^6A Promoting mRNA stability	ALKBH5/m^6A/PKMYT1/IGF2BP3	Oncogene	[74]
IGF1R	IGF2BP2	Reader	Promoting mRNA stability	m^6A/IGF1R/IGF2BP2/RhoA/ROCK	Oncogene	[90]
YAP1	METTL3	Writer	Enhancing m^6A which promotes mRNA translation	METTL3/m^6A/YAP1/TEAD	Oncogene	[91]
USP14	YTHDF1	Reader	Promoting mRNA translation	m^6A/USP14/YTHDF1	Oncogene	[92]
Nanog	ALKBH5	Eraser	Demethylating m^6A which promotes mRNA decay	lncNRON/ALKBH5/m^6A/Nanog	Oncogene	[104]
SPHK2	METTL3 YTHDF1	Writer Reader	Enhancing m^6A Promoting mRNA translation	METTL3/m^6A/SPHK2/YTHDF1/KLF2	Oncogene	[93]
HK2	WTAP	Writer	Enhancing m^6A which promotes mRNA stability	WTAP/m^6A/HK2	Oncogene	[94]
C-Jun	KIAA1429	Writer	Enhancing m^6A which promotes mRNA stability	KIAA1429/m^6A/c-Jun	Oncogene	[95]
Cyclin D1	METTL16	Writer	Enhancing m^6A which promotes mRNA stability	METTL16/m^6A/cyclin D1	Oncogene	[96]
FZD7	YTHDF1	Reader	Promoting mRNA translation	m^6A/FZD7/YTHDF1/β-catenin/TCF	Oncogene	[83]
MYC	METTL3 FTO	Writer Eraser	Enhancing m^6A which promotes mRNA translation Demethylating m^6A which promotes mRNA stability	HBXIP/METTL3/m^6A/MYC HDAC3/FOXA2/FTO/m^6A/MYC	Oncogene Oncogene	[64,80]
ZMYM1	METTL3 HuR	Writer Reader	Enhancing m^6A Promoting mRNA stability	METTL3/m^6A/ZMYM1/HuR/EMT	Oncogene	[62]
HDGF	METTL3 IGF2BP3	Writer Reader	Enhancing m^6A Promoting mRNA stability	P300/H3K27ac/METTL3/m^6A/HDGF/IGF2BP3	Oncogene	[65]
ARHGAP5	METTL3 HuR	Writer Reader	Enhancing m^6A Promoting mRNA stability	LncRNA ARHGAP5-AS1/METTL3/m^6A/ARHGAP5/HuR	Oncogene	[102]
CDCP1	METTL3	Writer	Enhancing m6A which promotes mRNA translation	EED/miR-338-5p/METTL3/m^6A/CDCP1	Oncogene	[105]
SEC62	METTL3 IGF2BP1	Writer Reader	Enhancing m^6A Promoting mRNA stability	miR-4429/METTL3/m^6A/SEC62/IGF2BP1	Oncogene	[106]
E2F3	MiR-660	miRNA	Silencing mRNA	miR-660/m^6A/E2F3	Oncogene	[84]
DDIT3	FTO	Eraser	Attenuating m^6A	FTO/m^6A/DDIT3	Suppressor	[113]
BATF2	METTL3	Writer	Enhancing m^6A which represses mRNA expression	METTL3/m^6A/BATF2/p53/ERK	Suppressor	[82]
PTEN	METTL3 YTHDF2	Writer Reader	Enhancing m^6A Promoting mRNA decay	LINC00470/METTL3/m^6A/PTEN/YTHDF2	Suppressor	[103]

Table 3. m⁶A-modified ncRNAs in GC.

ncRNA			m^6A Regulator		Function of Regulator	Pathway	Role of target	Reference
LINC01320	lncRNA		METTL14	Writer	Enhancing m^6A which upregulates lncRNA	METTL14/m^6A/LINC01320/miR-495-5p/RAB19	Oncogene	[89]
NEAT1	lncRNA		ALKBH5	Eraser	Demethylating m^6A	ALKBH5/m^6A/lncRNA NEAT1/EZH2	Oncogene	[93]
pri-miR-17-92	pri-miRNA		METTL3 DGCR8	WriterReader	Enhancing m^6A Facilitating processing of pri-miRNA	METTL3/m^6A/pri-miR-17-92/DGCR8/PTEN or TMEM127/mTOR	Oncogene	[97]
circORC5	circRNA		METTL14	Writer	Enhancing m^6A which inhibits circRNA expression	METTL14/m^6A/circORC5/miR-30c-2-3p/AKT1S1/EIF4B	Oncogene	[100]

Figure 2. Aberrant m⁶A promotes or inhibits GC by interacting with GC-related RNAs and regulating the corresponding pathways.

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