Cell Death Dis: SF3B1 regulates the maturation of KSR2 mRNA and promotes the development of endometrial cancer.

About 65,620 new cases of endometrial cancer are expected to be diagnosed in the United States by 2020, and 12,590 women are expected to die from the disease, making it one of the most common gynaecological malignancies.
the number of cases is expected to double by 2030 as obesity, a key risk factor for endometrial cancer, increases.
treatment options for the disease include endocrine therapy, chemotherapy, immunotherapy, radiotherapy and hysterectomy.
because endocrine therapy has limited efficacy, hysterectomy is not the most appropriate option for women who want to retain fertility.
, a deeper understanding of the genes associated with endometrial cancer development is conducive to the development of new disease treatment strategies.
to identify new prognosis and therapeutic targets, the researchers focused on a new area of the cancer: mRNA variable shearing, and studied the important role of the shear factor SF3B1 in the pathogenesis of endometrial cancer.
SF3B1 over-expression in endometrial cancer cells analyzed by tissue chips, the researchers found that people with higher levels of expression of SF3B1 protein in endometrial cancer than non-cancerous tissue.
addition, knocking down SF3B1 can reduce the proliferation, migration and invasion of endometrial cancer cells is ishkawa and AN3CA.
, the SF3B1 inhibitor PLAD-B (Pladienolide-B) reduces the proliferation and invasive effect of both cell lineages.
addition, PLAD-B inhibits tumor growth in in-place endometrial cancer mouse models.
PLAD-B inhibits the growth of endometrial cancer researchers identified about 2,000 differential expression genes (DEGs) associated with SF3B1 knock-down in endometrial cancer cells using RNA-Seq.
In addition, variable clipping (AS) event analysis shows that knocking out SF3B1 can cause multiple categories of AS events, including exon jumps (ES), transcription starting point variable clipping (TSS), and transcription termination site variable clipping (TTS).
SF3B1 regulates the maturation of KSR2 mRNA, and bio-information analysis of cell proliferation driven by KSR2 mediated SF3B1 shows that KSR2 is a potential candidate for endometrial cancer function mediated by SF3B1.
further studies have shown that knocking out SF3B1 lowers the expression level of KSR2 due to a reduction in the process from pre-mRNA prescions of KSR2 to mature RNA.
important, the researchers found that knocking down SF3B1 could save the expression of KSR2 and partially restore the growth of endometrial cancer cells.
in summary, the findings reveal that SF3B1 plays a vital carcinogenic role in the development of endometrial cancer, so SF3B1-related inhibitors may be used to treat the disease.
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