MiR-130b Is a Prognostic Marker and Inhibits Cell Proliferation and Invasion in Pancreatic Cancer through Targeting STAT3

Zhao, Gang; Zhang, Jungang; Shi, Ying; Qi, Qin; Liu, Yang; Wang, Bo; Tian, Kui; Deng, Shichang; Li, Xiang; Zhu, Shuai; Gong, Qiong; Niu, Yi; Wang, Chunyou

doi:10.1371/journal.pone.0073803

Cited by 110 publications

(91 citation statements)

References 36 publications

(35 reference statements)

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“…A long-term follow-up study of patients that had enhanced miR-130 expression suggested an association with poor prognoses. Zhao et al (18) observed that miR-130b expression was significantly decreased in pancreatic cancer, and a long-term follow-up study suggested that pancreatic cancer patients with low miR-130b expression had poor prognoses compared to pancreatic cancer patients with high miR-130b expression, suggesting that miR-130b shares features with tumor-suppressor genes.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, miR-130b was demonstrated to have tumor suppressive and cancer-promoting properties depending on the tumor type. miR-130b is highly expressed in melanoma (9), gastric (10), bladder (11) and colorectal cancer (12), esophageal squamous cell carcinoma (13) and glioma (14), but significantly and poorly expressed in papillary thyroid carcinomas (15), endometrial cancer (16), pituitary adenomas (17) and pancreatic cancer (18). Previously, miR-130b was observed to be overexpressed in glioma tissues, while the suppression of the expression of miR-130b via peroxisome proliferator-activated receptor-γ (PPAR-γ) inhibited the proliferation and invasive activity of glioma (14).…”

Section: Introductionmentioning

confidence: 99%

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miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD

Xiao

Yin

et al. 2017

Oncology Reports

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Abstract. MicroRNAs are short non-coding RNAs that play important roles in gliomas. However, the role of miR-130b in glioma remains unclear. In the present study, miR-130b expression was upregulated in glioma tissues and cell lines. Kaplan-Meier analysis indicated that the upregulation of miR-130b expression correlated with poor prognoses in glioma patients. Multivariate analysis demonstrated that this upregulation and a high-grade classification were independent factors that both predicted poor outcomes for glioma patients. Dual-luciferase assays identified that the cylindromatosis (CYLD) gene is a direct target of miR-130b. Functional studies demonstrated that a miR-130b mimic significantly promoted the growth and invasion of glioma cells, while also inhibiting apoptosis via selective targeting of CYLD, which was enhanced by CYLD-targeted siRNA. In contrast, a miR-130b inhibitor suppressed these biological behaviors, and this inhibition was reversed by CYLD-targeted siRNA. These data revealed that miR-130b could act as a novel potential diagnostic biomarker for glioma, while also demonstrating the importance of miR-130b in the cell proliferation and progression of glioma, indicating that it may serve as a useful therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD

Xiao

Yin

et al. 2017

Oncology Reports

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“…Activated STAT3 (phospho-STAT3 (p-STAT3)) in particular is constitutively overexpressed in several tumor types and is a negative prognostic factor for multiple cancers (34 -40). In pancreatic cancer, high expression of STAT3 is correlated with increased tumor size and stage and lymphatic metastasis (34), and the prognostic significance of microRNA-130b, which targets STAT3, was inversely correlated with STAT3 (35). The critical functional importance of STAT3 in cancer is aptly summarized in Ref.…”

Section: Stat2 Stat3 Stat4 Stat5a Stat5b and Stat6 (43)mentioning

confidence: 99%

Benzyl Isothiocyanate (BITC) Induces Reactive Oxygen Species-dependent Repression of STAT3 Protein by Down-regulation of Specificity Proteins in Pancreatic Cancer

Kasiappan

Jutooru²,

Karki

et al. 2016

Journal of Biological Chemistry

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Edited by Eric R. FearonThe antineoplastic agent benzyl isothiocyanate (BITC) acts by targeting multiple pro-oncogenic pathways/genes, including signal transducer and activator of transcription 3 (STAT3); however, the mechanism of action is not well known. As reported previously, BITC induced reactive oxygen species (ROS) in Panc1, MiaPaCa2, and L3.6pL pancreatic cancer cells. This was accompanied by induction of apoptosis and inhibition of cell growth and migration, and these responses were attenuated in cells cotreated with BITC plus glutathione (GSH). BITC also decreased expression of specificity proteins (Sp) Sp1, Sp3, and Sp4 transcription factors (TFs) and several pro-oncogenic Sp-regulated genes, including STAT3 and phospho-STAT3 (pSTAT3), and GSH attenuated these responses. Knockdown of Sp TFs by RNA interference also decreased STAT3/pSTAT3 expression. BITC-induced ROS activated a cascade of events that included down-regulation of c-Myc, and it was also demonstrated that c-Myc knockdown decreased expression of Sp TFs and STAT3. These results demonstrate that in pancreatic cancer cells, STAT3 is an Sp-regulated gene that can be targeted by BITC and other ROS inducers, thereby identifying a novel therapeutic approach for targeting STAT3. Isothiocyanates (ITCs)3 are a family of structurally related natural products that are found in cruciferous vegetables such as glucosinolates, which are hydrolyzed by the enzyme myrosinase to give the unconjugated ITCs. Cruciferous vegetables in the diet have been associated with decreased risks for human cancers and exhibit both chemoprevention and chemotherapeutic activities in animal models, and this has primarily been associated with ITCs (1-5). Sulforaphane, allyl isothiocyanate, phenethyl isothiocyanate (PEITC), and benzyl isothiocyanate (BITC) have been extensively investigated as anticancer agents, and a recent review summarizes the multiple genes and associated pathways activated by ITCs (4). Treatment of cancer cells or animal models that develop tumors with ITCs decreases cell growth, induces apoptosis, and inhibits epithelial-to-mesenchymal transition, angiogenesis, and cell cycle progression (6 -16). ITCs, including BITC, exhibit a broad spectrum of activities that include induction of ROS and ROS-regulated genes, direct inhibition of genes, and formation of peptide and protein adducts (4,5,(15)(16)(17). ITCs form adducts with both thiol and amino groups, and the formation of amino adducts forms the basis of the Edman procedure used in protein sequencing (15, 18 -20). Many of these ITC-induced effects contribute to their anticancer activities; however, a recent study suggests that the alkylation of peptides by ITCs may also be responsible for allergic skin reactions to these compounds (20).Studies in this laboratory have focused on specificity protein (Sp) transcription factors (TFs) Sp1, Sp3, and Sp4 as non-oncogene addiction genes in cancer cells, and knockdown of Sp1, Sp3, and Sp4 individually and combined inhibits cell growth, induces apoptosis, and inhibi...

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“…miR-124 also inhibited HCC cell growth by directly targeting STAT3 (42). In pancreatic cancer, miR-130b decreased cell growth and invasion via inhibition of STAT3 (43). In gastric cancer, miR-874 targeted the STAT3/vascular endothelial growth factor A signaling pathway and functioned as a tumor suppressor (44).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-125b targeted STAT3 to inhibit laryngeal squamous cell carcinoma cell growth and motility

et al. 2017

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Abstract.A majority of studies have indicated that microRNA-125b (miR-125b) is aberrantly expressed in various types of cancer. However, there are no studies on the expression and function of miR-125b in human laryngeal squamous cell carcinoma (LSCC). In the present study, miR-125b expression in LSCC sample tissues, corresponding adjacent non-neoplastic tissues, LSCC cell lines and a normal human keratinocyte cell line was measured using the reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-125b mimics, the Cell Counting Kit-8, cell migration, cell invasion, western blotting and dual-luciferase reporter assays were performed on LSCC cell lines. According to the results, miR-125b was observed to be significantly downregulated in LSCC, and its expression was significantly associated with clinical stage and alcohol history. miR-125b was also observed to decrease cell growth, migra tion and invasion in LSCC cells by directly targeting signal transducer and activator of transcription 3. The results of the present study suggested that miR-125b may be a potential treatment target of LSCC in the future.

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MiR-130b Is a Prognostic Marker and Inhibits Cell Proliferation and Invasion in Pancreatic Cancer through Targeting STAT3

Cited by 110 publications

References 36 publications

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD

miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD

Benzyl Isothiocyanate (BITC) Induces Reactive Oxygen Species-dependent Repression of STAT3 Protein by Down-regulation of Specificity Proteins in Pancreatic Cancer

MicroRNA-125b targeted STAT3 to inhibit laryngeal squamous cell carcinoma cell growth and motility

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