Serine 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 of SHMT2 gene 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 of SHMT2 by promoting the recognition of an
m6A site and the interaction of PTBP1/IGF2BP2 with SHMT2
mRNA. 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.