MiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTEN

Yang, Tianshe; Yang, Xinggang; Wang, Xudong; Wang, Yiling; Zhou, Bo; Zhang, Song

doi:10.1186/1475-2867-13-68

Cited by 139 publications

(145 citation statements)

References 27 publications

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“…Consistently, previous studies have considered miRNAs as important biomarkers and promising therapeutic targets for the treatment of various diseases (13). Recently, miR-214 was reported to be involved in certain types of cancer, including breast (14), adrenocortical (15), ovarian (16) and gastric cancer (17). Thus, the roles of miR-214 may be critical in the development of cancer.…”

Section: Introductionmentioning

confidence: 68%

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

Yang¹,

Chang²,

Zhao³

et al. 2015

Oncology Letters

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Abstract. MicroRNAs (miRNAs) are important gene regulators that participate in tumorigenesis. Previous studies have implicated that miR-214 is a tumor suppressor that is capable of inhibiting human hepatocellular carcinoma (HCC) cell growth. However, the mechanism by which miR-214 suppresses tumor development remains unknown. In the present study, miR-214 was observed to suppress tumor proliferation by directly targeting E2F transcription factor 3 (E2F3) in HCC cells. Colony formation, cell cycle and proliferation assays were employed to study the tumor suppressor role of miR-214 in cell proliferation. In addition, western blotting and dual-luciferase reporter assays were used to evaluate whether E2F3 was a target of miR-214. The results of these analyses revealed that E2F3 was a novel target of miR-214. Furthermore, enhanced expression of miR-214 or silencing of E2F3 inhibited the proliferation of HCC SMMC-7721 cells. These findings suggest that miR-214 suppresses HCC growth by targeting E2F3, and may provide a novel approach for the treatment of human HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common types of malignancy and the third leading cause of cancer-associated mortalities worldwide, due to its poor prognosis and frequent relapse and metastasis (1,2). Furthermore, HCC is difficult to treat, since it is usually diagnosed at advanced stages (3). Thus, studying the molecular mechanism of HCC in order to identify novel prognostic markers or therapeutic targets for the treatment of HCC is of value.MicroRNAs (miRNAs) are small noncoding RNAs of ~22 nucleotides (nt) in length that regulate gene expression at the post-transcriptional level (4). miRNAs are initially transcribed as long primary precursor molecules named pri-miRNAs, which are processed in a number of endonuclease reactions to produce the mature effector 22-nt miRNA molecule (5). Through the specific targeting of the 3'-untranslated regions (3'-UTRs) in the target genes of the miRNA, the translational repression and degradation of their target mRNA occurs (6). By targeting various transcripts, miRNAs are involved in a number of fundamental biological processes, including cell proliferation and differentiation, apoptosis, development and metabolism (7-9). Previous studies suggest that the expression of miRNAs is remarkably dysregulated in cancer, due to numerous epigenetic and genomic alterations (10,11). Several miRNAs have been demonstrated to act as tumor suppressor genes or oncogenes in tumors (12). As one miRNA may potentially regulate numerous mRNAs, it is clear that they are important regulatory molecules. Consistently, previous studies have considered miRNAs as important biomarkers and promising therapeutic targets for the treatment of various diseases (13). Recently, miR-214 was reported to be involved in certain types of cancer, including breast (14), adrenocortical (15), ovarian (16) and gastric cancer (17). Thus, the roles of miR-214 may be critical in the development of cancer.In the present study, bioinformatics...

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Section: Introductionmentioning

confidence: 68%

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

Yang¹,

Chang²,

Zhao³

et al. 2015

Oncology Letters

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“…38,49 Further, PTEN has also been shown to increase proliferation, migration, and invasion; in addition, it can cause apoptosis of PASMCs. 20,50 Potentially, derepression of PTEN in the lung of miR214 −/− mice may have initially induced increased remodeling but may have caused apoptosis in PASMCs in the remodeled vessels at later stages of the model. This may account for the effect observed on RVH but not on RVSP or remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…16 It can also function as both a tumor suppressor and an oncogene in various types of human cancer through influencing proliferation, migration, and apoptosis. [17][18][19][20] Therefore, though its effects may be varied, miR-214 can influence processes important in PAH in a cell type-specific manner.…”

mentioning

confidence: 99%

Regulation and Function of miR‐214 in Pulmonary Arterial Hypertension

et al. 2016

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Dysregulation of microRNAs (miRNAs) can contribute to the etiology of diseases, including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle (RV) in mice and rats exposed to the Sugen (SU) 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in pulmonary artery smooth muscle cells exposed to transforming growth factor β1 but not BMP4. We then examined miR-214 −/− mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in RV systolic pressure or remodeling observed between the miR-214 −/− and wild-type hypoxic groups. However, we observed a significant increase in RV hypertrophy (RVH) in hypoxic miR-214 −/− male mice compared with controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214 −/− mice. Thus, miR-214 stem loop loss leads to elevated RVH and may contribute to the heart failure associated with PAH. Pulmonary arterial hypertension (PAH) is a disease characterized by narrowing of the small pulmonary arteries, leading to vascular remodeling, an elevation in pulmonary artery pressure, right ventricular hypertrophy (RVH), and heart failure. 1 Current therapies for PAH aim to reverse the endothelial dysfunction and vasoconstriction observed. 2 However, despite these therapies, PAH mortality rates remain high, and the 3-year survival of patients is only 54.9%. 3 Changes in the pulmonary vasculature are the primary cause of PAH; however, right ventricle (RV) function is a major determinant of the severity of symptoms and prognosis of pulmonary hypertension. Many therapies in development for PAH are focused on targeting the RV since heart failure is the ultimate cause of mortality in PAH. 4 PAH is predominant in females, with female ∶ male ratios of 1.4-4.1 ∶ 1. 5 Sexual dimorphism has also been observed in RV failure. Female PAH patients exhibit improved RV ejection fraction and survival compared with men. 6 This could be due at least in part to the protective effect of estrogen on RV function. 7,8 MicroRNAs (miRNAs) are involved in multiple cellular responses during normal development and disease; they act as posttranscriptional regulators to fine-tune protein synthesis. Evidence has emerged for a key role for miRNA in regulation of the cellular processes involved in PAH. We previously demonstrated that a range of miRNAs are dysregulated in rats exposed to models of PAH. 9 Later studies have shown that miR-21, the miR-143/145 cluster, miR-27a, the miR-17-92 cluster, miR-124, miR-150, miR-138, miR-190, miR-204, miR-206, miR-210, and miR-328 play a role in the development of PAH. 10 Multiple miRNAs could potentially be targeted in concert as therapeutics in PAH. 11 MicroRNA miR-214 is transcribed as a bicistronic primary transcript, which is processed to generate 4 separate mature miRNAs...

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“…Proteins were purified with the NE-PER Nuclear and Cytoplasmic Protein Extraction Reagents Kit (Thermo Scientific) [20]. In brief, cells were lysed with lysis buffer and proteins were harvested.…”

Section: Western Blottingmentioning

confidence: 99%

“…Real-time quantitative PCR was done with Real-time PCR Universal Reagent and the MX3000P Real-time PCR instrument following the manufacturers' protocols [20]. All steps were repeated for 3 times.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

MicroRNA‐106b in cancer‐associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN

Yang

Chen

et al. 2014

FEBS Letters

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Edited by Varda Rotter Keywords:Cancer associated fibroblasts microRNA Protein tyrosine phosphatase and tensin homologue Gastric cancer a b s t r a c t It is well established that the interaction between cancer cells and microenvironment has a critical role in tumor development, but the roles of miRNAs in this interaction are rarely known. Here, we have shown that miR-106b is up-regulated in cancer associated fibroblasts compared with normal fibroblasts established from patients with gastric cancer, the expression level of miR-106b is associated with poor prognosis of patients, and CAFs with down-regulated miR-106b could significantly inhibit gastric cancer cell migration and invasion by targeting PTEN. Taken together, these data suggest that miR-106b might be a novel candidate target for the treatment of gastric cancer.

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MiR-214 regulate gastric cancer cell proliferation, migration and invasion by targeting PTEN

Cited by 139 publications

References 27 publications

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

MicroRNA-214 suppresses the proliferation of human hepatocellular carcinoma cells by targeting E2F3

Regulation and Function of miR‐214 in Pulmonary Arterial Hypertension

MicroRNA‐106b in cancer‐associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN

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