Endocrine Abstracts

Abstract: Somatostatin analogs (SSAs) constitute first-line treatment for patients with neuroendocrine tumors. Somatostatin receptors (SSTRs) are the most common therapeutic, radiotherapeutic, and imaging targets of SSAs. Some G-protein-coupled receptors, including SSTRs, regulate their responsiveness to continuous drug exposure with different degrees of receptor internalization. Thus, SSTR internalization seems to play an important role in predicting the response to SSAs in patients with neuroendocrine tumors. The present study aimed to regulate SSTR internalization via miRNA profiling after SSA (octreotide) treatment in the rat pancreatic beta cell line INS-1. INS-1 cells were treated with octreotide at various incubation times (0–60 min) to confirm SSTR internalization via immunofluorescence staining. Internalization of SSTR2 in INS-1 cells was induced after 5 min of SSA treatment. Hence, we analyzed the changes in microRNA expression between 0 and 5 min after octreotide treatment. Using a greater than two-fold change in cut-off for miRNA expression, 49 probe sets were up-regulated at 5 min versus at 0 min of incubation, and 75 were down-regulated. Interestingly, miRNA involved in ubiquitination, such as rno-miR-504, rno-miR-99a-5p, and rno-miR-466b-3 were up-regulated. In conclusion, we identified miRNAs responsible for SSTR2 internalization. To modulate SSTR internalization by miRNA in tumor cells of a patient, treatment with SSAs would be clinically relevant, as this could improve the response to therapy or for tumor detection.