Cancer mechanism research "missing puzzle" found

Original title: Research on Cancer Mechanism "Lack of Puzzle" found on the 23rd published on "Natural" magazine showed that the University of North Carolina Church Mountain Branch and North Carolina University Lenberg Integrated Cancer Center Researchers have discovered a new mechanism to activate a particular gene and cause cancer.

This study can open a new treatment path for attacking cancer cells. The new study shows that the mutation of the two unrelated genes can promote a process called "liquid-liquid phase separation", similar to the oil and water mixing, but the two cannot fully fuse.

The process occurs in the nucleus, and can form a compartment having various physical properties, resulting in a cancer such as acute leukemia.

  In order to understand this process, researchers have experimented experimenting with cancer cells carrying a common gene called NUP98-HOXA9.

This abnormal fusion is only present in blood cells in leukemia patients.

  The protein produced by Nup98-HOXA9 has a structureless extension, called the intrinsic disorder zone (IDR). The researchers found that when Nup98-HOXA9 proteins reached a critical value in the nucleus in the nucleus, IDRs promoted the liquid-liquid phase separation process, causing Nup98-HOXA9 to become staged or separated, so that Nup98-HOXA9 The protein is more closely coupled to DNA.

After the combination, a unique mode called super-enhancer is generated when the two is separated, which can make Nup98-HOXA9 fusion protein activity, resulting in invasive leukemia.

  At the same time, researchers have also found that NUP98-HOXA9 fusion proteins can affect the three-dimensional structure of the genome by creating a chromatogenic ring after separation of liquid-liquid phase. Dyed rings can help control the genome which areas are active, which areas are not active.

It can link its regulatory zone to the cancer gene to increase the expression and fatality of the cancer gene, thereby promoting cancer development. The researchers pointed out that this discovery is the first clear evidence of "phase separation" to form a chromatogenic ring.

  One of the main authors of this paper, Douglas Pash, Assistant Professor, Cell Biology and Physiology Assistant, North Carolina University Medical College, said that similar gene fusion was observed in other malignant tumors, the new mechanism found It can also be used to explain the reasons for other types of cancer development.

  Another main author, the school’s biochemistry, biophysics and pharmacology Associate Professor Greg King said: "’phase separation’ and its role in cancer has always been a lack of puzzle in cancer research." This process It is also possible to affect neurodegenerative diseases, such as Alzheimer’s disease, liquid-liquid phase separation may be part of the cause of plaque accumulation in the patient’s brain. In theory, a drug specifically destroys or dissolves this phase separation state may become new therapies.

(Zhang Jiaxin) (Question: Musheng Yu, Xu before).