The following is the summary of  “PIM1-Induced Cytoplasmic Expression of RBMY Mediates Hepatocellular Carcinoma Metastasis” published in the November 2022 issue of Cellular and Molecular Gastroenterology and Hepatology by Chua, et al.

Hepatocellular carcinoma (HCC) patients who have metastasized have a very poor prognosis. RNA binding motif Y-linked (RBMY) has been shown in our earlier research to be a possible biomarker for poor survival in HCC patients, but its role in metastasis is still mostly unknown. Patients with primary HCC were all male and a total of 308. Researchers used immunohistochemistry to follow RBMY expression from the onset of a primary HCC tumor to the development of distant metastasis, and investigators used a protein microarray to investigate upstream regulators of RBMY. To gain further functional insights on RBMY, a battery of metastasis assays was carried out in mice models and HCC cell lines.

 RBMY cytoplasmic expression was predictive of HCC metastasis in 82.4% of cases and was linked to fast distant metastasis (about 1 year after resection). Upon phosphorylation by the provirus integration in Moloney 1 (PIM1) kinase, RBMY provided strong migratory and invasive capacity. PIM1 binding to RBMY resulted in mutual stabilization and large translocation of RBMY from the nucleus to mitochondria, inhibiting mitochondrial apoptosis and increasing mitochondrial production of ATP and ROS, promoting cell motility. Reducing RBMY levels inhibited the transcription factor Snail1/zinc finger E-box binding. 1. dependent mitochondrial fission and dynamin-related protein 1–mediated epithelial-mesenchymal transition.

PIM1 inactivation and deletion reduced RBMY expression. Liver-to-lung metastasis was facilitated in nude mice by cytoplasmic RBMY through upregulation of epithelial-mesenchymal transition, mitochondrial proliferation, and mitochondrial fission, while RBMY localized to the nucleus blocked the mitochondrial switch and did not produce lung metastasis. This research demonstrated that PIM1-driven cytoplasmic expression of RBMY regulated HCC metastasis and proposed a novel therapeutic target for suppressing metastasis.

Source: sciencedirect.com/science/article/pii/S2352345X22002090