Somatostatin analogs, which are used to treat neuroendocrine tumors, inhibit hormone secretion or promote tumor shrinkage; however, their efficacy varies between patients, possibly because of differential expression of somatostatin receptors (SSTRs) in tumors. In this study, we evaluated the regulatory mechanism underlying the expression of SSTR2, the main octreotide target. Thirty miRNAs were found to be dysregulated in neuroendocrine cells (INS-1 cells) incubated with octreotide compared to that in placebo-treated cells. Among the upregulated miRNAs, miR-16-5p was elevated after short-term octreotide treatment. We conducted in vitro experiments to determine whether the expression of miR-16-5p was associated with the regulation of SSTR2 expression and affected octreotide sensitivity in INS-1 cells. Overexpression of miR-16-5p by transfected mimics induced upregulation of SSTR2 expression. Additionally, the expression of miR-16-5p further enhanced octreotide-induced reduction in cell proliferation in both two- and three-dimensional culture of INS-1 cells. Thus, our results reveal the mechanism underlying SSTR2 expression regulation and may aid in developing therapeutic approaches for enhancing the response to octreotide, particularly in patients unresponsive to SSTR2-targeted somatostatin analog treatment.
Bibliographical noteFunding Information:
Funding:Thisresearchwassupportedbythe NationalResearchFoundationofKorea(grant numbersNRF-2015R1D1A1A01057737andNRF- 2018R1C1B6003894)andIncheonNational UniversityResearchGrantin2018.
This research was supported by the National Research Foundation of Korea (grant numbers NRF-2015R1D1A1A01057737 and NRF-2018R1C1B6003894) and Incheon National University Research Grant in 2018.
© 2020 Jo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)