摘要：SummarySerine hydroxymethyltransferase 2 (SHMT2), which catalyzes the conversion of serine to glycine and one-carbon transfer reactions in mitochondria, is significantly upregulated in glioblastoma (GBM). However, the mechanism by which the stability ofSHMT2gene expression is maintained to drive GBM tumorigenesis has not been clarified. Herein, through microarray screening, we identified that HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) modulates the SHMT2 level in various GBM cell lines. Serine catabolism and mitochondrial oxidative phosphorylation activities were decreased by HOTAIRM1 inhibition. Mechanistically, according to our mass spectrometry and eCLIP-seq results, HOTAIRM1 can bind to PTBP1 and IGF2BP2. Furthermore, HOTAIRM1 maintains the stability ofSHMT2by promoting the recognition of an m6A site and the interaction of PTBP1/IGF2BP2 withSHMT2mRNA. The stability of HOTAIRM1 can also be enhanced and results in positive feedback regulation to support the progression of GBM. Thus, targeting HOTAIRM1 could be a promising metabolic therapy for GBM.Graphical abstractDisplay OmittedHighlights•HOTAIRM1 regulates mitochondrial activity in GBM•The target genes of HOTAIRM1 and the interacting RBPs were screened and identified•SHMT2mRNA has an m6A site that can be recognized by IGF2BP2•HOTAIRM1 regulates the stability ofSHMT2by binding to PTBP1 and IGF2BP2Cellular physiology; Cell biology; Cancer
