Targeting a non-encoding stretch of RNA may help shrink tumors caused by an aggressive type of brain cancer in children, according to new research in mice reported in Cell Reports.
Medulloblastoma are the most common type of malignant brain cancer in children. The most aggressive and difficult-to-treat form of the disease is group 3 medulloblastoma, which is often fatal. By targeting long, noncoding genetic material called lnc-RNAs that drive the expression of cancer-causing genes, the study’s senior author, and colleagues have demonstrated an innovative new approach that shrinks group 3 medulloblastoma tumors in mice.
“Group 3 medulloblastoma is very aggressive, and there are currently no targeted therapies,” says the senior author. “Our novel therapeutic approach based on noncoding RNA could fill an urgent need for new therapies for this devastating disease in children.”
RNA acts as a template for building proteins based on instructions encoded in the DNA. Until recently, scientists thought 97% of RNA was “junk” because only 3% is used to build proteins. However, scientists have realized that RNA’s nonprotein encoding stretches control gene expression. A previous study by the authors showed that a long noncoding stretch of RNA called lnc-HLX-2-7 contributes to the growth of group 3 medulloblastoma tumors by attaching to a DNA promoter that increases expression of cancer-causing genes. Promoters are nongene coding stretches of DNA adjacent to genes that act like switches turning them on.
The new study provides additional details showing that lnc-HLX-2-7 specifically binds to the HLX promoter region of DNA, increasing HLX gene expression and causing the tumor to grow. HLX triggers tumor growth by binding to promoter regions for several other cancer-causing genes, increasing their expression. One gene that HLX increases expression of is MYC, which also increases the expression of several other cancer-causing genes, causing a cascade of activity that accelerates the growth of group 3 medulloblastoma tumors.
The team developed an intravenous treatment to block lnc-HLX-2-7 from binding to the HLX promoter to stop this cascade of cancer-gene expression. They assembled a sequence of nucleotides (called antisense oligo nucleotides), the building blocks of RNA, that can bind to the corresponding nucleotides that make up lnc-HLX-2-7, preventing it from binding to the HLX promoter in the DNA and leading to its destruction. They coated the sequence with microscopic particles called cerium oxide nanoparticles to protect the lnc-HLX-2-7 until it reaches its target.
When the team treated a mouse model of group 3 medulloblastoma with the experimental intravenous therapy, it reduced tumor growth by 40%–50%. Adding cisplatin, a chemotherapy drug currently used to treat medulloblastomas, alongside the new therapy caused the tumors to shrink even more and prolonged the animals’ survival. The combination therapy extended the animals’ lives by about 84 days compared with a 44-day increase in survival on lnc-HLX-2-7 alone.
“When you combine the two treatments, you see dramatic effects,” the author says.
The team plan studies of the therapy in humans to further test its safety and efficacy.
“Understanding why MYC is elevated in these tumors is extremely important, and this new link to HLX provides insights that open new therapeutic possibilities,” says study co-author.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00266-3
Latest News
How the brain fine-tunes it…
By newseditor
Posted 25 Apr
Immune cells carry a long-l…
By newseditor
Posted 25 Apr
Mutations in noncoding DNA…
By newseditor
Posted 24 Apr
More influence of environme…
By newseditor
Posted 24 Apr
The assembly of the human c…
By newseditor
Posted 24 Apr
Other Top Stories
A pair of brain regions prompts females to kill or care for their y…
Read more
Neurotic people are more likely to suffer from mood swings
Read more
Positive parenting buffers stress's effects on the brain
Read more
How the brain judges time
Read more
Fear is in the eye of the beholder
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Thiol dioxygenases: from st…
By newseditor
Posted 27 Apr
Systematic characterization…
By newseditor
Posted 27 Apr
The MYCN 50 UTR as a therap…
By newseditor
Posted 25 Apr
Control of neuronal excitat…
By newseditor
Posted 25 Apr
Epithelial UNC-23 limits me…
By newseditor
Posted 25 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar