MKNK2 (MAPK Interacting Serine/Threonine Kinase 2)

BRIX1 activated by mTORC1-SP1 signaling regulates ribosome biogenesis and AS to promote HCC progression. Our findings establish BRIX1 as a governor on both ribosome biogenesis and AS in HCC, and a possible prognostic or therapeutic biomarker.

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.

The nude mouse IRFA model further validated the above molecular mechanisms. This study reveals for the first time the key regulatory role of the miR-1180-3p/MKNK2/CREB3 signaling axis in CRLM recurrence after IRFA, providing a molecular theoretical basis for preventing rapid progression of CRLM after RFA.

These findings suggest that SRSF1 plays a key role in CCA by regulating apoptosis and autophagy. Its silencing promotes cancer cell death, partly by correcting oncogenic splicing errors, making it a potential target for CCA treatment.

Finally, our main finding was that combined treatment with SP600125 and radiotherapy reduced the resistance of metastatic tetraploid cells to treatment, essentially by inhibiting the JNK pathway. This result supports a promising anti-cancer strategy to overcome the resistance of tetraploid cancer cells to irradiation.

The abnormal expression of MKNK2 is associated with tumor progression, immune checkpoint genes, immune cell infiltration, microsatellite instability (MSI), tumor mutational burden (TMB), and stemness in a variety of tumors, especially in glioblastoma multiforme low-grade gliomas (GBMLGG). Therefore, MKNK2 may serve as a potent prognostic physiological marker and provide new avenues for the development of tumor mechanisms and therapeutic strategies targeting MKNK2 to enhance the efficacy of immunotherapy.

The ADCP-based signature may serve as a new option for prognosis prediction and the personalized treatment of GC patients.

miR-125b acts as a suppressive factor in multiple myeloma and can affect the malignant behavior of MM by regulating the expression of MKNK2.

We identified 5 (8.8 %) novel potential driver in-frame fusion genes, MKNK2::MOB3A, ICMT::RPS6KA3, ATP1B3::GRK7, CSNK2A1::KIF16B, and FGFR3::MAEA, and 1 (1.8 %) known in-frame fusion gene, FGFR3::TACC3, in 57 patients with pharyngeal carcinoma. Our results suggest that sporadic fusion genes may contribute to tumorigenesis in oropharyngeal carcinomas.

Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

Overall, our investigation underscored the profound implications of SGMS2, a gene pivotal to NK cell infiltration, in the landscape of HCC, thereby positioning it as a potential linchpin in oncological strategies.

Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.