Newly identified THOR gene could play a role in suppressing tumors

Inhibiting a gene called THOR may help limit the growth and spread of melanoma cells.

Scientists at the University of Michigan Comprehensive Cancer Center were drilling down into the human genome when they discovered a novel gene—one that also appears to be active in zebrafish and mice. That degree of conservation among species is rare, so they figured it must be important.

In fact, the newly identified gene plays a role in cancer development, so inhibiting it could lead to new ways of shrinking tumors. They published their findings in the journal Cell.

The group found a "long noncoding RNA" (lncRNA) that is particularly active in testes cells. So they called it THOR—short for Testis-associated Highly-conserved Oncogenic long noncoding RNA. By studying THOR in zebrafish and mouse models, the University of Michigan team discovered that it’s highly expressed in lung cancer and melanoma cells, too. After further investigation, they found that if they knocked down THOR in the cancer cells, the growth of tumors slowed down. If they boosted it, cancer growth accelerated.

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But when they eliminated THOR from normal cells, nothing happened. That suggests the IncRNA may only have an influence on cancer cells. The gene’s association with a Marvel superhero is perfectly appropriate, they believe, because it may be possible to target THOR with drugs that attack cancer cells but leave the good guys alone.

lncRNAs were previously believed to be of little importance, but in 2015, the Michigan researchers identified thousands that they believed should be studied further. “Most of the ones we test don't have a clear function” like THOR does, said pathology professor and team leader Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, in a press release.

Chinnaiyan’s team hopes to create a compound that can bind with THOR and then touch off a sequence of events that will deplete it from cancer cells. This approach, called antisense oligonucleotides, is already well-known in biotech. Atlantic Healthcare recently started a rolling submission for FDA approval of its antisense drug to treat inflammatory bowel disease, and Ionis recently licensed a similar drug to Johnson & Johnson’s Janssen for global development. Ionis is also developing three antisense drugs targeting cancer.

The University of Michigan researchers became more and more optimistic about knocking down THOR with antisense as they learned more about how it functions. They discovered, for example, that THOR influences proteins called IGFBPs, which are believed to be important in cancer because they stabilize RNA. “If we perturb THOR function, we disturb the ability to stabilize RNA. This inhibits cell proliferation," Chinnaiyan said.