Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5

Zhang, Junfeng; Xu, Kun; Shi, Lili; Zhang, Li; Zhao, Zhaohua; Xu, Hao; Liang, Fei; Li, Hongbo; Zhao, Yan; Xu, Xi; Tian, Yingfang

doi:10.3727/096504017x14874323871217

Cited by 19 publications

(23 citation statements)

References 54 publications

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“…To test the hypothesis whether modification of beta cell miRNA profile could promote their proliferation, we chose miR-216a, which has been shown to relate to cell proliferation by a number of investigators [37][38][39][42][43][44] . The PCR and ISH data confirmed the miRNA microarray findings that the expression of miR-216a in pancreatic islets increased during the development of T1D, which could be a compensatory mechanism used by the damaged beta cells.…”

Section: Discussionmentioning

confidence: 99%

miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model

Wang

Liu

Zhao

et al. 2020

Sci Rep

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Aberrant expression of miRNAs in pancreatic islets is closely related to the development of type 1 diabetes (T1D). The aim of this study was to identify key miRNAs dysregulated in pancreatic islets during T1D progression and to develop a theranostic approach to modify their expression using an MRI-based nanodrug consisting of iron oxide nanoparticles conjugated to miRNA-targeting oligonucleotides in a mouse model of T1D. Isolated pancreatic islets were derived from NOD mice of three distinct age groups (3, 8 and 18-week-old). Total RNA collected from cultured islets was purified and global miRNA profiling was performed with 3D-Gene global miRNA microarray mouse chips encompassing all mouse miRNAs available on the Sanger miRBase V16. Of the miRNAs that were found to be differentially expressed across three age groups, we identified one candidate (miR-216a) implicated in beta cell proliferation for subsequent validation by RT-PCR. Alterations in miR-216a expression within pancreatic beta cells were also examined using in situ hybridization on the frozen pancreatic sections. For in vitro studies, miR-216a mimics/inhibitors were conjugated to iron oxide nanoparticles and incubated with beta cell line, βTC-6. Cell proliferation marker Ki67 was evaluated. Expression of the phosphatase and tensin homolog (PTEN), which is one of the direct targets of miR-216a, was analyzed using western blot. For in vivo study, the miR-216a mimics/inhibitors conjugated to the nanoparticles were injected into 12-week-old female diabetic Balb/c mice via pancreatic duct. The delivery of the nanodrug was monitored by in vivo MRI. Blood glucose of the treated mice was monitored post injection. Ex vivo histological analysis of the pancreatic sections included staining for insulin, PTEN and Ki67. miRNA microarray demonstrated that the expression of miR-216a in the islets from NOD mice significantly changed during T1D progression. In vitro studies showed that treatment with a miR-216a inhibitor nanodrug suppressed proliferation of beta cells and increased the expression of PTEN, a miR-216a target. In contrast, introduction of a mimic nanodrug decreased PTEN expression and increased beta cell proliferation. Animals treated in vivo with a mimic nanodrug had higher insulinproducing functionality compared to controls. These observations were in line with downregulation of PTEN and increase in beta cell proliferation in that group. Our studies demonstrated that miR-216a could serve as a potential therapeutic target for the treatment of diabetes. miR-216a-targeting theranostic nanodrugs served as exploratory tools to define functionality of this miRNA in conjunction with in vivo MR imaging.

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Section: Discussionmentioning

confidence: 99%

miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model

Wang

Liu

Zhao

et al. 2020

Sci Rep

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“…However, increasing studies have suggested that glioma‐associated miRNAs function as tumor suppressors by interfering with Wnt/β‐catenin. For instance, miRNA‐216a impedes glioma cell proliferation, migration, and invasion, and these events are closely linked with the suppression of Wnt/β‐catenin signaling (J. Zhang, Xu, et al, ). Both miR‐202 and miR‐139‐5p attenuate the malignant phenotypes of glioma cell by the inhibitory effect of Wnt/β‐catenin pathway, as mentioned earlier (Q. Wang, Xu, et al, ; J. Yang, Fan, Zhao, & Fang, ).…”

Section: Multiple Roles Of Mirna Regulatory Wnt/β‐catenin Signaling Imentioning

confidence: 99%

“…Consistently, miR-96/HBP1/ Wnt/β-catenin regulatory circuitry promotes the proliferation of glioma cells(Yan et al, 2014).However, increasing studies have suggested that glioma-associated miRNAs function as tumor suppressors by interfering with Wnt/β-catenin. For instance, miRNA-216a impedes glioma cell proliferation, migration, and invasion, and these events are closely linked with the suppression of Wnt/β-catenin signaling (J Zhang, Xu, et al, 2017)…”

mentioning

confidence: 99%

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

Zhou

Zeng

et al. 2018

Journal Cellular Physiology

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Glioma is one of the most treatment‐refractory intracranial tumors, and the aberrant expressed Wnt/β‐catenin pathway is closely associated with glioma malignancy. In this regard, Wnt/β‐catenin signaling has been reported to play an essential role in cellular proliferation, migration, invasion, and angiogenesis, therefore contributing to glioma progression. However, the underlying mechanisms of Wnt/β‐catenin signaling involvement in gliomagenesis remain unknown. Here, we present an overview of the Wnt components and then go on to summarize the current knowledge describing the multitude of roles of Wnt/β‐catenin in glioma, which are mediated by transcription factors, microRNAs, long noncoding RNAs, and so on. In the latter portion of the review, we elaborate the increasing apparent crosstalk of Wnt/β‐catenin pathway with PI3K/AKT signaling involved in these processes. Ultimately, compounds targeting the Wnt/β‐catenin are described in glioma. As better understanding of the regulatory mechanisms to glioma malignancies increases, Wnt/β‐catenin cascade may represent an area of developmental glioma therapeutics focus.

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“…Aberrant miRNA expression is strongly correlated with the development of metastasis in various cancers, including GC [ 9 ]. miR-216a has recently been reported to play a tumor suppressive role in human cancer including glioma [ 10 ], colorectal cancer (CRC)[ 11 ] and pancreatic cancer [ 12 , 13 ]. miR-216a suppresses invasion, migration and proliferation of glioma cells by inhibiting leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)[ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…miR-216a has recently been reported to play a tumor suppressive role in human cancer including glioma [ 10 ], colorectal cancer (CRC)[ 11 ] and pancreatic cancer [ 12 , 13 ]. miR-216a suppresses invasion, migration and proliferation of glioma cells by inhibiting leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)[ 10 ]. Furthermore, miR-216a prohibits invasion and migration of CRC cells in vitro , and restrains liver metastasis in vivo by targeting KIAA1199 [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting JAK2/STAT3-mediated EMT process

Tao

Yang

et al. 2017

Oncotarget

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MicroRNAs (miRNAs), a group of small, non-protein coding, endogenous RNAs, play critical roles in the tumorigenesis and progression of human cancer. miR-216a has recently been reported to play an oncogenic role in human cancer. While, the expression of miR-216a, its biological function and underlying molecular mechanisms in gastric cancer (GC) are largely unknown. In this study, we revealed that miR-216a was underexpressed in GC tissues compared to matched noncancerous tissues. Decreased levels of miR-216a were confirmed in GC cell lines compared with a normal gastric epithelium cell line. miR-216a underexpression was associated with malignant prognostic features including lymph node metastasis, venous infiltration, invasive depth and advanced TNM stage. GC patients with low miR-216a level showed an obvious shorter overall survival. miR-216a overexpression restrained migration and invasion of MGC-803 cells, while its knockdown exerted opposite effects on metastatic behaviors of SGC-7901 cells. In vivo experiments found that miR-216a restoration reduced metastatic nodes of GC cells in nude mice liver. miR-216a notably suppressed epithelial-mesenchymal transition (EMT) of GC cells. Janus kinase 2 (JAK2) was recognized as a direct target and downstream mediator of miR-216a in GC cells. Interestingly, JAK2/signal transducer and activator of transcription 3 (STAT3) pathway was prominently inactivated by miR-216a and probably mediated the role of miR-216a in the regulation of migration, invasion and EMT process of GC cells. In conclusion, these data suggest that miR-216a functions as a tumor suppressive miRNA in the development of GC possibly by targeting JAK2/STAT3-mediated EMT.

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Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5

Cited by 19 publications

References 54 publications

miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model

miR-216a-targeting theranostic nanoparticles promote proliferation of insulin-secreting cells in type 1 diabetes animal model

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

MicroRNA-216a inhibits the metastasis of gastric cancer cells by targeting JAK2/STAT3-mediated EMT process

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