PLEKHA1 (Pleckstrin Homology Domain Containing A1)

Specifically, QKI was found to modulate the splicing of PLEKHA1 exon 15, a cancer-specific AS biomarker, while SRSF1 regulated the splicing of MKNK2 exon 14, a subtype-specific AS biomarker. Our study provides valuable insights into key AS events and their regulatory mechanisms in lung cancer, paving the way for potential therapeutic targets.

Moreover, EphA2 inhibitors dasatinib and ALW II-41-27 remarkably suppress the progression of tumors expressing PLEKHA1-TACC2 in vivo. Functionally, PLEKHA1-TACC2 fusion and Trp53 deletion significantly increases tumor incidence, tumor multiplicity, and mouse mortality in transgenic ESCC mouse model, which could be suppressed by regorafenib, a EphA2 inhibitor approved by FDA in solid tumors. Together, our data indicate that PLEKHA1-TACC2 fusion protein has oncogenic activities and serves as a promising prognosis marker and therapeutic target.

This work identifies new genes that influence ageing and AD pathogenesis, and highlights the importance of microglia and oligodendrocytes in the resilience of the brain against ageing and AD pathogenesis. Our findings have implications for developing markers indicating the physiological age of the brain and new targets for therapeutic intervention.

Finally, we constructed a mouse subcutaneous tumor model and found that HHIP inhibited tumor proliferation and densification. In summary, HHIP in CAFs can regulate the JAK1/STAT3 pathway and affect the secretion of inflammatory factors, thus affecting the proliferation of PCa.

Importantly, the synergistic effects of EIF4G2 depletion and PLEKHA1 reduction in inhibiting cell migration and invasion underscore the therapeutic potential of targeting this axis. This study not only advances our understanding of translational regulation in HCC but also identifies the EIF4G2-PLEKHA1 axis as a promising therapeutic target, offering new avenues for intervention in HCC treatment.

ConclusionsIn conclusion, our transcriptomic study revealed a small set of 9 genes that distinguished an untreated CLL patient who underwent a prolonged periods of total fasting and maintained a slow-growing tendency of lymphocytosis, in comparison to 5 untreated CLL patients with a varied diet. Future investigations of patient #1 could demonstrate the potential role of prolonged periodic fasting and the involvement of the 9 genes in sustaining the trend of lymphocytosis and the benign course of the disease.

In conclusion, our transcriptomic study showed a small set of nine genes which characterized an untreated CLL patient, who followed a prolonged fasting period and maintained a slow-growing tendency of lymphocytosis, compared to 5 untreated CLL patients with a varied diet. Future investigations of patient #1 could demonstrate the potential role of prolonged periodic fasting and the involving of the nine genes in maintaining the trend of lymphocytosis and the benign course of the disease.

This study unveiled a small gene expression signature consisting of nine genes that distinguished an untreated CLL patient who followed prolonged periods of total fasting, maintaining a gradual growth trend of lymphocytosis, compared to five untreated CLL patients with a varied diet. Future investigations focusing on patient #1 could potentially shed light on the role of prolonged periodic fasting and the implication of this specific gene signature in sustaining the lymphocytosis trend and the favorable course of the disease.