Novel molecular mechanisms of glioblastoma (GBM)

Dual and separable functions of a lncRNA in GBM




Some lncRNAs promote the growth of cancer cells.  

An interesting type of lncRNA is one that is the "host" transcript of microRNAs (miRNAs).  

These are called lnc-pri-miRNAs.  

lnc-pri-miRNA transcripts are processed into miRNAs by DROSHA/DGCR8 (cartoon from Quinn and Chang, Nat Rev Genet, 2016)



lnc-pri-miRNA LOC646329


LOC646329 is the host transcript for miR29a/b1.

Knockdown of LOC646329 inhibits GBM growth.  But this is not because miR29 production is reduced.  Genetic removal of miR29a/b1 actually increases the malignancy of GBM!  We discovered that LOC646329 promotes the expression of the MKLN1 oncogene through DNA looping, enhancer-like activity (He et al., PNAS 2021).   

lnc-pri-miRNA loci are highly enriched for such enhancer-like characteristics.  

LOC646329 produces miRNAs that regulate apoptosis.  But this locus also forms DNA looping interactions with the MKLN1 oncogene, regulating cell proliferation. These two functions are genetically separable. 


Some ongoing research...

  • What are the protein-interacting partners of LOC646329?
  • Does LOC646329 (the green clouds below) form phase-separated condensates that function in gene regulation?
LOC646329 transcripts in the nucleus of GBM cells.