miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation

Egelí, Ünal; Tezcan, Gülçin; Çeçener, Gülşah; Tunca, Berrin; Sevinc, Elif Demirdogen; Kaya, Ekrem; Ak, Seçil; Dündar, Halit Ziya; Sarkut, Pınar; Uğraş, Nesrin; Yerci, Ömer; Ozen, Yilmaz; Evrensel, Türkkan

doi:10.1097/mpa.0000000000000640

Cited by 16 publications

(15 citation statements)

References 26 publications

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“…miRNAs have been identified to play a vital role in tumourigenesis since they can participate in many biological processes, such as cell proliferation, differentiation and invasion in a variety of cancer types. The loss of miR-216b expression has been reported in liver and breast cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma and colorectal cancer (19)(20)(21)(22)(23). It was reported that miR-216b inhibited cell proliferation, metastasis and invasion by regulating PKC-α and KRAS in nasopharyngeal carcinoma (24), and Hbx-miR-216b-IGF2bP2 signaling pathway in hepatocellular carcinoma (22).…”

Section: Discussionmentioning

confidence: 99%

miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1

Zhang

et al. 2017

Oncology Reports

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MicroRNAs (miRNAs) play a vital role in tumour biological and pathologic processes. In the present study, we aimed to detect the expression and biological role of miR-216b in glioma. Our data showed that miR-216b was significantly downregulated in human glioma tissues and cells. Ectopic expression of miR-216b inhibited the proliferation and invasion of U87 and U251 cells and suppressed the growth of xenograft tumours in vivo. Bioinformatic and luciferase reporter analyses identified Forkhead box protein M1 (FoxM1) as a direct target of miR-216b. Overexpression of miR-216b inhibited the expression of FoxM1 in glioma cells. Rescue experiments demonstrated that co-transfection of FoxM1 lacking the 3'-untranslated region partially prevented miR‑216b-induced inhibition of glioma cell growth and invasion. In vivo studies indicated that ectopic expression of miR-216b impeded the proliferation of glioma xenograft tumours in nude mice, coupled with a decreased in FoxM1 protein expression and the percentage of Ki-67-positive tumour cells. Taken together, our results provide evidence of the suppressive activity of miR‑216b in glioma, which is largely ascribed to downregulation of FoxM1. Restoration of miR-216b may provide a novel potential therapeutic agent for glioma.

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Section: Discussionmentioning

confidence: 99%

miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1

Zhang

et al. 2017

Oncology Reports

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“…Additionally, in human gastric adenocarcinoma, miR-216b is down-regulated and inhibits proliferation and cell cycle progression 17 . Moreover, Egeli U et al 18 found that reduced miR-216b expression was associated with aggressive tumor characteristics and shortened disease-free survival, suggesting the involvement of miR-216b in pancreatic cancer progression. Nevertheless, the role of miR-216b in the regulation of pancreatic cancer progression has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by Targeting TPT1 in Pancreatic Cancer Cells

You¹,

Tan²,

Gong³

et al. 2017

J. Cancer

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MicroRNAs (miRNAs) are increasingly recognized as being involved in pancreatic cancer progression by directly regulating the expression of their targets. In this study, we showed that miR-216b-5p expression was significantly decreased in pancreatic cancer tissues and cell lines. In addition, low miR-216b-5p expression was significantly associated with large tumor size and advanced TNM stage. Meanwhile, both Kaplan-Meier and multivariate survival analysis showed that decreased miR-216b-5p expression was associated with overall survival. miR-216b-5p over-expression repressed pancreatic cancer cell proliferation and induced cell cycle arrest and cell apoptosis in vitro and inhibited tumorigenesis in vivo. The translationally controlled tumor protein (TPT1) was identified as a novel direct target of miR-216b-5p. miR-216b-5p up-regulation suppressed TPT1 expression. Moreover, TPT1 mRNA expression levels were increased in pancreatic cancer tissues, and were inversely correlated with miR-216b-5p expression. TPT1 down-regulation had similar effects as miR-216b-5p up-regulation on pancreatic cancer cell progression. The restoration of TPT1 reversed the effect of miR-216b-5p on pancreatic cancer cell progression. Furthermore, we found that miR-216b-5p up-regulation suppressed Pim-3, Cyclin B1, p-Bad and Bcl-xL protein expression. However, the effect of miR-216b-5p up-regulation was partly reversed by TPT1 up-regulation in vitro. Taken together, our findings suggested that miR-216b-5p functions as a potential tumor suppressor by regulating TPT1 in pancreatic cancer cells, and it may represent a potential therapeutic target for patients with pancreatic cancer.

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“…miR-216b levels were shown to be lower in patients with hepatocellular carcinoma, and higher expression is associated with increased 5-year survival (Liu et al, 2015). miR-216b-5p targets FGFR1 in pancreatic cancer cells, and decreased expression is a marker for poor prognosis in pancreatic patients (Egeli et al, 2016).…”

Section: Regulation Of Ugt2b Expression and Activity By Mir-216b-5pmentioning

confidence: 99%

Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines

Dluzen

Sutliff

Chen

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds, including many hormones, drugs, and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction algorithm programs were used to screen for microRNAs (miRNAs) as potential regulators of UGT2B enzymes, with miR-216b-5p identified as a potential candidate. Luciferase data suggested the presence of a functional miR-216b-5p binding motif within the 39 untranslated regions of UGTs 2B7, 2B4, and 2B10. Overexpression of miR-216b-5p mimics significantly repressed UGT2B7 (P , 0.001) and UGT2B10 (P 5 0.0018) mRNA levels in HuH-7 cells and UGT2B4 (P , 0.001) and UGT2B10 (P 5 0.018) mRNA in Hep3B cells. UGT2B7 protein levels were repressed in both HuH-7 and Hep3B cells in the presence of increasing miR-216b-5p concentrations, corresponding with significant (P , 0.001 and P 5 0.011, respectively) decreases in glucuronidation activity against the UGT2B7-specific substrate epirubicin. Inhibition of endogenous miR-216b-5p levels significantly increased UGT2B7 mRNA levels in HuH-7 (P 5 0.021) and Hep3B (P 5 0.0068) cells, and increased epirubicin glucuronidation by 85% (P 5 0.057) and 50% (P 5 0.012) for HuH-7 and Hep3B cells, respectively. UGT2B4 activity against codeine and UGT2B10 activity against nicotine were significantly decreased in both HuH-7 and Hep3B cells (P , 0.001 and P 5 0.0048, and P 5 0.017 and P 5 0.043, respectively) after overexpression of miR-216b-5p mimic. This is the first evidence that miRNAs regulate UGT 2B7, 2B4, and 2B10 expression, and that miR-216b-5p regulation of UGT2B proteins may be important in regulating the metabolism of UGT2B substrates.

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miR-216b Targets FGFR1 and Confers Sensitivity to Radiotherapy in Pancreatic Ductal Adenocarcinoma Patients Without EGFR or KRAS Mutation

Cited by 16 publications

References 26 publications

miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1

miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1

MicroRNA-216b-5p Functions as a Tumor-suppressive RNA by Targeting TPT1 in Pancreatic Cancer Cells

Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines

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