Fig. 6: Hypoxia-induced regulation of CXCL10 expression by m6A demethylases in gastric cancer cells.
a Detection of m6A modification sites in CXCL10 mRNA in AGS cells following ALKBH5 knockdown, identified by pum6a analysis. b, c, d, e Knockdown of ALKBH5 upregulated CXCL10 mRNA expression in AGS cells (b, c) and MKN28 cells (d, e) under hypoxic conditions. In b, *p = 0.013, **p = 0.0086, by a t-test. In c, **p = 0.0098, **p = 0.0061, *p = 0.0103, ***p = 0.0001, by a t-test. In d, ***p = 0.0003, **p = 0.002, by a t-test. In e, *p = 0.029, *p = 0.0153, *p = 0.0129, ***p = 0.0004, by a t-test. f, g, h, i Knockdown of FTO upregulated CXCL10 mRNA expression in AGS cells (f, g) and downregulated CXCL10 expression in MKN28 cells (h, i) under hypoxia. In f, ***p = 0.0001, ***p = 0.0002, by a t-test. In g, ****p < 0.0001, ****p < 0.0001, *p = 0.0219, *p = 0.0147, by a t-test. In h, ****p < 0.0001, ****p < 0.0001, by a t-test. In i, **p = 0.0012, ***p = 0.0005, **p = 0.0041, **p = 0.0026, by a t-test. j, k, l, m ELISA validation of CXCL10 protein levels in AGS cells (j, k) and MKN28 cells (l, m) with ALKBH5 or FTO knockdown under normoxic and hypoxic conditions. In k, ***p = 0.0002, ****p < 0.0001, *p = 0.012, **p = 0.0021, by a t-test. In m, ***p = 0.0003, ***p = 0.0003, **p = 0.0031, *p = 0.0356, by a t-test. n, o, p, q Actinomycin D chase assays showing that ALKBH5 knockdown decelerated CXCL10 mRNA decay rates in AGS cells (n, o) and MKN28 cells (p, q) under hypoxia. In o, ****p < 0.0001, by a two-way ANOVA; In q, **p = 0.0024, by a two-way ANOVA. r, s, t, u FTO Knockdown decreased CXCL10 mRNA decay rates in AGS cells (r, s) under hypoxia but promoted mRNA stability in MKN28 cells (t, u). In s, ***p = 0.0003, by a two-way ANOVA. Data are presented as mean ± S.D.  and are representative of three independent experiments. Source data are provided as a Source Data file.
