MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2

Feng, Shujun; Pan, Wenjing; Jin, Yue; Zheng, Jie

doi:10.1007/s13277-014-2546-0

Cited by 63 publications

(50 citation statements)

References 25 publications

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“…Moreover, many miRNAs, such as miR-25, miR-181b, and miR-93, suppressed LATS2 at the posttranscription level by directly binding to its mRNA in multiple cancer cells (41)(42)(43). Our results demonstrated that LATS2 could be regulated at the transcriptional level through histone modification mediated by lncRNA PVT1 and PRC2.…”

Section: Discussionmentioning

confidence: 66%

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

Wan

Sun

Liu

et al. 2016

Molecular Cancer Therapeutics

209

180

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Long noncoding RNAs (lncRNA) are a novel class of transcripts with no protein coding capacity, but with diverse functions in cancer cell proliferation, apoptosis, and metastasis. The lncRNA PVT1 is 1,716 nt in length and located in the chr8q24.21 region, which also contains the myelocytomatosis (MYC) oncogene. Previous studies demonstrated that MYC promotes PVT1 expression in primary human cancers. However, the expression pattern and potential biologic function of PVT1 in non-small cell lung cancer (NSCLC) is still unclear. Here, we found that PVT1 was upregulated in 105 human NSCLC tissues compared with normal samples. High expression of PVT1 was associated with a higher tumor-node-metastasis stage and tumor size, as well as poorer overall survival. Functional analysis revealed that knockdown of PVT1 inhibited NSCLC cell proliferation and induced apoptosis both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that PVT1 recruits EZH2 to the large tumor suppressor kinase 2 (LATS2) promoter and represses LATS2 transcription. Furthermore, ectopic expression of LATS2 increased apoptosis and repressed lung adenocarcinoma cell proliferation by regulating the Mdm2-p53 pathway. Taken together, our findings indicated that PVT1/EZH2/LATS2 interactions might serve as new target for lung adenocarcinoma diagnosis and therapy.

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Section: Discussionmentioning

confidence: 66%

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

Wan

Sun

Liu

et al. 2016

Molecular Cancer Therapeutics

209

180

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“…Such a reduction in the mRNA expression of LATS2 is likely to be induced by mechanisms other than promoter hypermethylation. Previously, several micoRNAs, including microRNA (miR)93 in breast cancer (13), miR25 in ovarian cancer (14) and miR31 in lung (15) and endometrial cancer (16), have been reported to directly target the LATS2 gene and reduce its anti-oncogenic effect. A previous study identified a LATS2 mutation, which can reduce the expression of the gene in lung cancer, however, such a mutation in breast cancer remains to be elucidated (2,3).…”

Section: Discussionmentioning

confidence: 99%

LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

et al. 2017

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Abstract. Tumor-specific promoter hypermethylation of large tumor suppressor, homolog 2 (LATS2), a tumor suppressor gene, has been investigated using methylation-specific polymerase chain reaction (MSP) assays in different types of human cancer producing conflicting results. The aim of the present study was to evaluate the methylation status of the LATS2 promoter region using bisulfite sequencing with a next generation sequencer for breast cancer. In the 11 patients enrolled in the present study, the LATS2 promoter methylation index (MI) was uniformly high in tumor and normal tissues of the breast (median, 84.0 and 87.4%, respectively). The presence of LATS2 promoter hypermethylation was confirmed in isolated tumor cells and normal epithelial cells using the magnetic-activated cell sorting method. In situ hybridization for LATS2 messenger RNA (mRNA) revealed that the mRNA expression of LATS2 was higher in normal epithelial cells, compared with tumor cells, however, it was not significantly associated with LATS2 MI. In 12 breast cancer cell (BCC) lines and two normal breast cell lines, the LATS2 promoter was uniformly hypermethylated with no correlation between the mRNA expression of LATS2 and the LATS2 MI. In addition, treatment of the BCC lines with a demethylating reagent had minimal effect on the mRNA expression of LATS2 in any of these cell lines. These results demonstrated that LATS2 hypermethylation was not involved in silencing the mRNA expression of LATS2 mRNA. The lower mRNA expression level of LATS2 in tumor cells, compared with normal epithelial cells, suggested the possible involvement of downregulation in the mRNA expression of LATS2 in the pathogenesis of breast cancer. Therefore, the conflicting results previously reported for LATS2 promoter methylation in different types of cancer, detected using MSP assays may be attributable to the low fidelity of the MSP assay. IntroductionLarge tumor suppressor, homolog 2 (LATS2), is a tumor suppressor gene implicated in the regulation of cell proliferation, migration and apoptosis via several cell signaling pathways, particularly the Hippo, p53 and LATS-LIM domain kinase-actin pathways (1). Classically, a tumor suppressor gene is inactivated by a somatic mutation or promoter hypermethylation. Previous human cancer genome projects have revealed the presence of LATS2 mutations in several types of human cancer, including breast cancer, however, its frequency is low at ~1% (2,3). Therefore, LATS2 mutations are unlikely to be important in the pathogenesis of the majority of breast cancer cases. By contrast, hypermethylation of the LATS2 promoter has been reported in a higher proportion of breast cancer (50%) (4), acute lymphoblastic leukemia (ALL) (24%) (5), astrocytoma (71.5%) (6), lung cancer (78.8%) (7), and nasopharyngeal cancer (36.7%) (8) cases, and the absence of LATS2 hypermethylation has been confirmed in normal breast tissues (4) and normal brain tissues (6). In addition, the association between LATS2 promoter hypermethylation and reduced messenger RNA ...

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“…Due to their small size and influence in a broad range of biological processes, miRNAs are very attractive therapeutic targets for GBM. miR-25 is one of the most overexpressed miRNAs in a number of profiling experiments designed for the detection of miRNAs dysregulated in human cancers [16][17][18][19][20][21][22][23][24][25]29]. Li et al reported that miR-25 promoted gastric cancer migration, invasion, and proliferation by directly targeting transducer of ERBB2 and 1 and correlated with poor survival [17].…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18][19][20][21][22][23][24][25]. However, the role of miR-25 in glioblastoma tumorigenesis and the underlying molecular mechanisms by which miR-25 exerts its functions had remained-until recently-largely unknown.…”

Section: Introductionmentioning

confidence: 99%

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

Peng

Yuan

et al. 2015

Mol Cell Biochem

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Glioblastoma multiforme (GBM) is the most malignant and common brain tumor; it is aggressive growth pattern means that GBM patients face a poor prognosis even when receiving the best available treatment modalities. In recent years, an increasing number of reports suggest that the discovery of microRNAs (miRNAs) might provide a novel therapeutic target for human cancers, including GBM. One miRNA in particular, microRNA-25 (miR-25), is overexpressed in several cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-25 in GBM has not been totally elucidated. In this study, we demonstrated that miR-25 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. In vitro studies further demonstrated that overexpressed miR-25 was able to promote, while its antisense oligos inhibited cell proliferation and invasion in U251 cells. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target molecule of miR-25. Also of note was the fact that NEFL was down-regulated with increased levels of miR-25 expression in human astrocytoma clinical specimens. In addition, via the mTOR signaling pathway, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-25 on the proliferation and invasion of U251 cells. Overall, our results showed an important role for miR-25 in regulating NEFL expression in GBM, and suggest that miR-25 could be a potential target for GBM treatment.

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MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2

Cited by 63 publications

References 25 publications

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

Long Noncoding RNA PVT1 Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

LATS2 promoter hypermethylation and its effect on gene expression in human breast cancer

miR-25 promotes glioblastoma cell proliferation and invasion by directly targeting NEFL

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