The mRNA and protein expression of their target gene MAP4K4 were upregulated in SAN treated xenotransplanted tumors, and pMEK4 and pJNK1 proteins in the MAPK/JNK signaling pathway were also upregulated by SAN.
These results suggest that downregulation of miR-98-5p promotes tumor development by downregulation of MAP4K4 and inhibition of the downstream MAPK/ERK signaling, thus, highlighting the potential of miR-98-5p as a therapeutic target for PDAC.
The parallel increase of c-Met and MAP4K4 expression in SHH MB could predict an increased potential of these tumors to infiltrate brain tissue and cause metastatic disease.
When clinicopathological characteristics were assessed, cytoplasmic NIK was associated with survival (p = 0.014), whereas cytoplasmic RelB was associated with increased tumor grade (p = 0.020) and decreased inflammation (p = 0.019).
Using the specific 185-gene signature generated by unsupervised consensus clustering of gene expression data, we defined four subtypes associated with distinct clinical metrics: tumors with high metastasis associated with EMT (epithelial to mesenchymal transition) and active MAP4K4/JNK signaling pathway; tumors with high chromosomal instability with up regulated MYC targes; well differentiated tumors with less aggressive and moderated tumors.
We previously reported that STRN4 directly associated with protein kinases, such as MINK1, TNIK and MAP4K4, which are associated with tumor suppression or tumor progression.
Therefore, we conclude that miR-141 targets MAP4K4, acts as a tumor suppressor in pancreatic cancer cells, and may serve as a novel therapeutic agent for miRNA-based pancreatic cancer therapy.