Confirmed UTX is a cancer-suppressing gene (EXITS) that escapes X chromosome inactivation

On July 13, the international academic journal Nature Communications published its latest research from the Jiang Hai Research Group of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences: UTX is an escape X-inactivation tumor-suppressor in B cellmphoma.
the study, which has experimentally confirmed that UTX is the cancer-suppressing gene (EXITS) that escapes X chromosome inactivation, which may be one of the reasons why men have a higher incidence and mortality rate of cancer than women.
at the same time, the research work found that UTX inactivation in tumor initiation, development and anti-tumor drug response in the important impact of malignant lymphoma early diagnosis and tumor resistance molecular basis and efficacy evaluation provides an important theoretical basis.
a large number of clinical studies show that the incidence of many tumors has significant gender differences, and the incidence of cancer and mortality is significantly higher in men than in women.
to explain this phenomenon, several scholars have proposed the theory of cancer-suppressing gene (EXITS) to escape X chromosome inactivation based on the variant of the cancer-suppressing gene associated with the X chromosome in human cancer genome data.
the theory, there are some potential anti-cancer genes on the X chromosome, because they escape the X chromosome inactivation mechanism through special means, so that women's two copies of the X chromosome anti-cancer gene can be expressed, and has anti-cancer function.
so in women, two copies of the anti-cancer gene are inactivated to allow cancer to occur, while men have only one X chromosome, and the inactivation of a single copy of the X-chromosome anti-cancer gene allows cancer to occur.
this may be one of the major causes of gender disparities in cancer incidence. Genes such as UTX on the
X chromosome scann higher frequencies of mutations and deletions in cancer and are presumed to be important candidates for these phenomena, the Escape from X-Inactivation Tumor.
in this study, Jiang Hai's team reported utX as a direct experimental evidence of the cancer suppressor gene (EXITS) that escaped X chromosome inactivation, and with the help of the mouse spontaneous lymphoma model, the study found that the UTX copy number showed significant dose effect during tumor occurrence, which strongly supported the EXITS theory.
more importantly, UTX knockout not only accelerates the occurrence of lymphoma, but also significantly promotes the development of lymphoma.
high expression of lymphoma in mice models, UTX knockout mice had higher levels of malignant lymphoma, brain aggression and more pronounced vascular formation. further studies
found that in human lymphoma and mouse lymphoma, UTX inactivated tumors over-expression of the factor Efnb1, which affects cell adhesion and migration.
expression of Efnb1 in lymphoma cell lines can lead to malignant phenotypes such as brain aggression and angiogenesis.
findings provide new explanations for understanding how UTX inactivation promotes malignancy of tumors and the molecular mechanisms of lymphoma brain metastasis.
finally, for the first time, a joint lethal analysis of chemotherapy drugs already used in clinical use for the utx-defective tumors found that UTX inactivated lymphoma cells were highly sensitive to the chemotherapy drug Cytarabine, providing a new direction for precision treatment of lymphoma.
postdoctoral student Li Xiaoxuan (now working at Jiangsu University School of Medicine) is the first author of the paper, researcher Jiang Hai is the author of the newsletter, and Zhang Yanli, a member of the research group, has done a lot of work in mouse breeding.
the study was greatly assisted by Dr. Chen Degui and Dr. Zheng Liyuan of the Institute of Biochemistry and Cell, in the utX knockout of mice, and thanked Dr. Zhao Jingxuan and Wei Zhuang for their assistance.
the project has been funded by the national key research and development program, the Chinese Academy of Sciences pilot special, the National Natural Science Foundation and other funds, and also by the chemical and biological center public technical service center animal experimental technology platform, cell biology technology platform technical support.
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