Cell Death Dis: Blocking the hypusination effect of EIF5A inhibits the growth of colorectal cancer cells

Colorectal cancer (CRC), the world's third deadliest and fourth most commonly diagnosed cancer, usually starts with benign adenoma-based pyrocarcinoma and develops into a highly atypically proliplative advanced adenoma, which eventually develops into an immersive cancer.
in the early stages of the disease, cancer cells are restricted to the colon wall and the disease can be cured by surgical removal.
as the cancer progresses, the cancer cells reach the regional lymph nodes through the colon wall, where about 70% of CRC cases can be cured through a combination of surgery and complementary chemotherapy.
when the cancer reaches advanced stage, the cancer cells move from place to place, resulting in poor prognosis, and the average survival rate of patients with current treatments is only 25-30 months.
although there has been some progress in CRC-related molecular mechanisms, the current treatment plan includes only a few drugs with limited efficacy, and the overall survival rate of patients is not satisfactory.
, it is particularly important to identify potential therapeutic targets for the disease.
pattern diagram EIF5A is a translation starting factor regulated by hypusination (serotonin lysine), a unique post-translation modification of DHPS and DOHH catalysis started with polyamine.
latest research data show that hypusined EIF5A regulates a range of key cellular processes such as autophagy, aging, polyamine stabilization, and energy metabolism, and works in cancer.
, however, little is known about the inhibition of EIF5A in preclinical cancer models, the molecular mechanisms involved, and specific translation targets.
results show that hypusined EIF5A promotes the growth of CRC cells by directly regulating the biosynthetics of MYC in a specific suspended state.
hypusination of EIF5A is inhibited by the knock-down effect of DHPS, lyovirus-mediated DHPS, or EIF5A, which inhibits the growth of CRC cells.
gene expression spectrum showed that inhibition of DHPS can reduce the expression of MYC multi-gene expression analysis showed that the inhibition of hypusination effect would impair the expression of transcripts of MYC regulation.
further confirmed that EIF5A regulates the synthesis of MYC primarily by reducing the stasis of five different suspended syndicates in MYC CDS without affecting their mRNA levels or protein stability.
Notably, the researchers found that in the preclinical model of CRC, blocking the hypusination effect caused significant growth inhibition and significantly reduced the size of the dipherone in the familial adenoma pharynoma (FAP) APCMin/plus mouse model.
, the above study data reveal an unprecedented molecular mechanism in which hypusined EIF5A's tumor-promoting properties are associated with its ability to regulate MYC synthesis.
results also provide some theoretical basis for the use of DHPS/EIF5A inhibitors in CRC treatment.
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