Somatostatin analogue treatment primarily induce miRNA expression changes and up-regulates growth inhibitory miR-7 and miR-148a in neuroendocrine cells

TY - JOUR

T1 - Somatostatin analogue treatment primarily induce miRNA expression changes and up-regulates growth inhibitory miR-7 and miR-148a in neuroendocrine cells

AU - Døssing, Kristina B.V.

AU - Kjær, Christina

AU - Vikeså, Jonas

AU - Binderup, Tina

AU - Knigge, Ulrich

AU - Culler, Michael D.

AU - Kjær, Andreas

AU - Federspiel, Birgitte

AU - Friis-Hansen, Lennart

PY - 2018

Y1 - 2018

N2 - Somatostatin (SST) analogues are used to control the proliferation and symptoms of neuroendocrine tumors (NETs). MicroRNAs (miRNA) are small non-coding RNAs that modulate posttranscriptional gene expression. We wanted to characterize the miRNAs operating under the control of SST to elucidate to what extent they mediate STT actions. NCI-H727 carcinoid cell line was treated with either a chimeric SST/dopamine analogue; a SST or dopamine analogue for proliferation assays and for identifying differentially expressed miRNAs using miRNA microarray. The miRNAs induced by SST analogue treatment are investigated in carcinoid cell lines NCI-H727 and CNDT2 using in situ hybridization, qPCR and proliferation assays. SST analogues inhibited the growth of carcinoid cells more potently compared to the dopamine analogue. Principal Component Analysis (PCA) of the samples based on miRNA expression clearly separated the samples based on treatment. Two miRNAs which were highly induced by SST analogues, miR-7 and miR-148a, were shown to inhibit the proliferation of NCI-H727 and CNDT2 cells. SST analogues also produced a general up-regulation of the let-7 family members. SST analogues control and induce distinct miRNA expression patterns among which miR-7 and miR-148a both have growth inhibitory properties.

AB - Somatostatin (SST) analogues are used to control the proliferation and symptoms of neuroendocrine tumors (NETs). MicroRNAs (miRNA) are small non-coding RNAs that modulate posttranscriptional gene expression. We wanted to characterize the miRNAs operating under the control of SST to elucidate to what extent they mediate STT actions. NCI-H727 carcinoid cell line was treated with either a chimeric SST/dopamine analogue; a SST or dopamine analogue for proliferation assays and for identifying differentially expressed miRNAs using miRNA microarray. The miRNAs induced by SST analogue treatment are investigated in carcinoid cell lines NCI-H727 and CNDT2 using in situ hybridization, qPCR and proliferation assays. SST analogues inhibited the growth of carcinoid cells more potently compared to the dopamine analogue. Principal Component Analysis (PCA) of the samples based on miRNA expression clearly separated the samples based on treatment. Two miRNAs which were highly induced by SST analogues, miR-7 and miR-148a, were shown to inhibit the proliferation of NCI-H727 and CNDT2 cells. SST analogues also produced a general up-regulation of the let-7 family members. SST analogues control and induce distinct miRNA expression patterns among which miR-7 and miR-148a both have growth inhibitory properties.

KW - Cancer

KW - Let-7

KW - MiR-148a

KW - MiR-7

KW - MiRNAs

KW - Neuroendocrine tumors

KW - Somatostatin analogues

U2 - 10.3390/genes9070337

DO - 10.3390/genes9070337

M3 - Journal article

C2 - 29973528

AN - SCOPUS:85049970758

SN - 2073-4425

VL - 9

JO - Genes

JF - Genes

IS - 7

M1 - 337

ER -