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The World Health Organization's International Agency for Research on Cancer (IARC) global cancer statistics show that in 2020, the number of new cases of colorectal cancer worldwide was 1.
93 million (the third highest incidence rate), and the number of colorectal cancer deaths was 935,000 (the highest mortality rate).
Second place) [1]
.
Although great progress has been made in the treatment of colorectal cancer, the incidence and mortality of colorectal cancer are still at the forefront of all types of cancer, and are increasing year by year
.
Therefore, there is an urgent need to study the molecular mechanisms underlying the development of colorectal cancer in order to develop more effective treatments
.
On March 25, 2022, Nature Communications published online the paper PUMILIO proteins promote colorectal cancer growth via the collaborative team of Prof.
Lin Haifan from Yale University, Prof.
Liu Sanhong from ShanghaiTech University (now a professor at Shanghai University of Traditional Chinese Medicine) and Prof.
Fang Chao from Shanghai Jiaotong University.
suppressing p21, this study found that PUMILIO protein directly binds to the 3'UTR (untranslated region) of cyclin-dependent protein kinase inhibitor p21 through PRE (Pumilio Response Element) to inhibit its expression, thereby promoting the occurrence and development of colorectal cancer
.
PUMILIO protein is an evolutionarily highly conserved RNA-binding protein whose RNA recognition domain is located at the carbon terminus and consists of 8 repeating sequences in tandem
.
The main mode of action of PUMILIO proteins is to inhibit translation by recognizing and binding to specific sequences on the target mRNA
.
PUMILIO plays an important role in the maintenance of germinal stem cell stemness and the development of the nervous system [2, 3].
Now more and more researchers have found that PUMILIO is involved in the occurrence and development of a variety of diseases, but its role in tumors is still limited.
Action and regulatory mechanisms are still poorly understood
.
Human genes encode two PUMILIO homologous proteins, PUM1 and PUM2 [4]
.
In colorectal cancer clinical samples, the researchers found that the expression of PUM1 and PUM2 was significantly higher in tumor tissues than in paired paracancerous tissues
.
Using the AOM/DSS colorectal cancer mouse model, the researchers found that intestinal epithelium-specific knockout of PUM1 and PUM2 significantly reduced tumor number and size in the AOM/DSS model, indicating that the loss of PUM1 and PUM2 can inhibit the development of colorectal cancer and development
.
Correspondingly, the researchers found that PUM1 and PUM2 were highly expressed in most colorectal cancer cell lines, and knockdown or knockout of PUM1 and/or PUM2 resulted in reduced tumorigenicity in vivo, slower growth in vitro, and inhibition of PUM1 and/or PUM2.
Transition of colorectal cancer cells from G1 phase to S phase
.
In order to further explore the mechanism of PUM protein in colorectal cancer, the researchers combined transcriptome, proteome, photoactivity-enhanced ribonucleoside cross-linking and co-immunoprecipitation and other molecular biological techniques to reveal that PUM1 directly binds p21 mRNA to regulate the growth of colorectal cancer cells
.
In addition, intravenous injection of nanoparticles carrying PUM1 and PUM2 siRNA significantly inhibited tumor growth in a mouse orthotopic colorectal cancer model, but did not affect the normal physiological functions of mice
.
In conclusion, the researchers found that PUMILIO protein is necessary for the occurrence and development of colorectal cancer, and identified p21 as the direct target gene of PUM1 protein in colorectal cancer cells
.
This study reveals a new function of PUMILIO protein in cancer, providing a new intervention and therapeutic target for colon cancer
.
Professor Lin Haifan, Professor Liu Sanhong and Professor Fang Chao are the co-corresponding authors of the paper, Gong Yuanyuan, Liu Zukai, Yuan Yihang and Yang Zhenzhen are the co-first authors of the paper, and Dr.
Zhang Jiawei, Lu Qin and Dr.
Wang Wei are the important participating authors of the paper
.
Original link: https:// Publisher: Eleven References 1.
Sung, H.
, et al.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA: a cancer journal for clinicians 71, 209-249 (2021).
2.
Lin, H.
& Spradling, AC A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary.
Development (Cambridge, England) 124, 2463-2476 (1997).
3.
Zhang, M.
, et al.
Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins.
Genes Dev 31, 1354-1369 (2017).
4.
Uyhazi, KE, et al.
Pumilio proteins utilize distinct regulatory mechanisms to achieve complementary functions required for pluripotency and embryogenesis.
Proc Natl Acad Sci USA 117, 7851-7862 (2020).
Reprint notice [non-original article] The copyright of this article belongs to the article All the author, welcome to forward and share personally, it is forbidden to reprint without permission, the author has all legal rights, and offenders must be prosecuted
.
93 million (the third highest incidence rate), and the number of colorectal cancer deaths was 935,000 (the highest mortality rate).
Second place) [1]
.
Although great progress has been made in the treatment of colorectal cancer, the incidence and mortality of colorectal cancer are still at the forefront of all types of cancer, and are increasing year by year
.
Therefore, there is an urgent need to study the molecular mechanisms underlying the development of colorectal cancer in order to develop more effective treatments
.
On March 25, 2022, Nature Communications published online the paper PUMILIO proteins promote colorectal cancer growth via the collaborative team of Prof.
Lin Haifan from Yale University, Prof.
Liu Sanhong from ShanghaiTech University (now a professor at Shanghai University of Traditional Chinese Medicine) and Prof.
Fang Chao from Shanghai Jiaotong University.
suppressing p21, this study found that PUMILIO protein directly binds to the 3'UTR (untranslated region) of cyclin-dependent protein kinase inhibitor p21 through PRE (Pumilio Response Element) to inhibit its expression, thereby promoting the occurrence and development of colorectal cancer
.
PUMILIO protein is an evolutionarily highly conserved RNA-binding protein whose RNA recognition domain is located at the carbon terminus and consists of 8 repeating sequences in tandem
.
The main mode of action of PUMILIO proteins is to inhibit translation by recognizing and binding to specific sequences on the target mRNA
.
PUMILIO plays an important role in the maintenance of germinal stem cell stemness and the development of the nervous system [2, 3].
Now more and more researchers have found that PUMILIO is involved in the occurrence and development of a variety of diseases, but its role in tumors is still limited.
Action and regulatory mechanisms are still poorly understood
.
Human genes encode two PUMILIO homologous proteins, PUM1 and PUM2 [4]
.
In colorectal cancer clinical samples, the researchers found that the expression of PUM1 and PUM2 was significantly higher in tumor tissues than in paired paracancerous tissues
.
Using the AOM/DSS colorectal cancer mouse model, the researchers found that intestinal epithelium-specific knockout of PUM1 and PUM2 significantly reduced tumor number and size in the AOM/DSS model, indicating that the loss of PUM1 and PUM2 can inhibit the development of colorectal cancer and development
.
Correspondingly, the researchers found that PUM1 and PUM2 were highly expressed in most colorectal cancer cell lines, and knockdown or knockout of PUM1 and/or PUM2 resulted in reduced tumorigenicity in vivo, slower growth in vitro, and inhibition of PUM1 and/or PUM2.
Transition of colorectal cancer cells from G1 phase to S phase
.
In order to further explore the mechanism of PUM protein in colorectal cancer, the researchers combined transcriptome, proteome, photoactivity-enhanced ribonucleoside cross-linking and co-immunoprecipitation and other molecular biological techniques to reveal that PUM1 directly binds p21 mRNA to regulate the growth of colorectal cancer cells
.
In addition, intravenous injection of nanoparticles carrying PUM1 and PUM2 siRNA significantly inhibited tumor growth in a mouse orthotopic colorectal cancer model, but did not affect the normal physiological functions of mice
.
In conclusion, the researchers found that PUMILIO protein is necessary for the occurrence and development of colorectal cancer, and identified p21 as the direct target gene of PUM1 protein in colorectal cancer cells
.
This study reveals a new function of PUMILIO protein in cancer, providing a new intervention and therapeutic target for colon cancer
.
Professor Lin Haifan, Professor Liu Sanhong and Professor Fang Chao are the co-corresponding authors of the paper, Gong Yuanyuan, Liu Zukai, Yuan Yihang and Yang Zhenzhen are the co-first authors of the paper, and Dr.
Zhang Jiawei, Lu Qin and Dr.
Wang Wei are the important participating authors of the paper
.
Original link: https:// Publisher: Eleven References 1.
Sung, H.
, et al.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA: a cancer journal for clinicians 71, 209-249 (2021).
2.
Lin, H.
& Spradling, AC A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary.
Development (Cambridge, England) 124, 2463-2476 (1997).
3.
Zhang, M.
, et al.
Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins.
Genes Dev 31, 1354-1369 (2017).
4.
Uyhazi, KE, et al.
Pumilio proteins utilize distinct regulatory mechanisms to achieve complementary functions required for pluripotency and embryogenesis.
Proc Natl Acad Sci USA 117, 7851-7862 (2020).
Reprint notice [non-original article] The copyright of this article belongs to the article All the author, welcome to forward and share personally, it is forbidden to reprint without permission, the author has all legal rights, and offenders must be prosecuted
.
