Dataset Information

NEAT1 regulates pancreatic cancer cell growth, invasion and migration though mircroRNA-335-5p/c-met axis.

ABSTRACT: NEAT1 has been reported to affect cancer progression, which was subsequently confirmed in multiple cancers. Hsa-miRNA-335-5p (miR-335-5p) has recently been identified as an anticancer agent in various organs. However, the relationship between NEAT1 and miR-335-5p remains poorly understood. In this study, we investigated the effects of NEAT1 and miR-335-5p on development of pancreatic cancer. The ectopic expression of miR-335-5p in pancreatic cancer cell lines significantly suppressed cell growth by inhibiting c-met. In addition, downregulating NEAT1 upregulates miR-335-5p. Taken together, our results demonstrate that the NEAT1/miR-335-5p/c-met axis plays a pivotal role in pancreatic cancer by regulating the proliferation, metastasis, and apoptosis of pancreatic cancer cells in vivo and in vitro.

SUBMITTER: Cao J

PROVIDER: S-EPMC5088299 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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NEAT1 regulates pancreatic cancer cell growth, invasion and migration though mircroRNA-335-5p/c-met axis.

Cao Jia J Zhang Yi Y Yang Jiachun J He Sijia S Li Mingming M Yan Shiyan S Chen Ying Y Qu Chunying C Xu Leiming L

American journal of cancer research 20161001 10

NEAT1 has been reported to affect cancer progression, which was subsequently confirmed in multiple cancers. Hsa-miRNA-335-5p (miR-335-5p) has recently been identified as an anticancer agent in various organs. However, the relationship between NEAT1 and miR-335-5p remains poorly understood. In this study, we investigated the effects of NEAT1 and miR-335-5p on development of pancreatic cancer. The ectopic expression of miR-335-5p in pancreatic cancer cell lines significantly suppressed cell growth ...[more]

PMID: 27822425

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Project description:BackgroundMultiple aberrant microRNA expression has been reported in gastric cancer. Among them, microRNA-335-5p (miR-335), a microRNA regulated by DNA methylation, has been reported to possess both tumor suppressor and tumor promoter activities.ResultsHerein, we show that miR-335 levels are reduced in gastric cancer and significantly associate with lymph node metastasis, depth of tumor invasion, and ultimately poor patient survival in a cohort of Amerindian/Hispanic patients. In two gastric cancer cell lines AGS and, Hs 746T the exogenous miR-335 decreases migration, invasion, viability, and anchorage-independent cell growth capacities. Performing a PCR array on cells transfected with miR-335, 19 (30.6%) out of 62 genes involved in metastasis and tumor invasion showed decreased transcription levels. Network enrichment analysis narrowed these genes to nine (PLAUR, CDH11, COL4A2, CTGF, CTSK, MMP7, PDGFA, TIMP1, and TIMP2). Elevated levels of PLAUR, a validated target gene, and CDH11 were confirmed in tumors with low expression of miR-335. The 3'UTR of CDH11 was identified to be directly targeted by miR-335. Downregulation of miR-335 was also demonstrated in plasma samples from gastric cancer patients and inversely correlated with DNA methylation of promoter region (Z = 1.96, p = 0.029). DNA methylation, evaluated by methylation-specific PCR assay, was found in plasma from 23 (56.1%) out of 41 gastric cancer patients but in only 9 (30%) out of 30 healthy donors (p = 0.029, Pearson's correlation). Taken in consideration, our results of the association with depth of invasion, lymph node metastasis, and poor prognosis together with functional assays on cell migration, invasion, and tumorigenicity are in accordance with the downregulation of miR-335 in gastric cancer.ConclusionsComprehensive evaluation of metastasis and invasion pathway identified a subset of associated genes and confirmed PLAUR and CDH11, both targets of miR-335, to be overexpressed in gastric cancer tissues. DNA methylation of miR-335 may be a promissory strategy for non-invasive approach to gastric cancer.

Dataset Information

NEAT1 regulates pancreatic cancer cell growth, invasion and migration though mircroRNA-335-5p/c-met axis.

Publications

NEAT1 regulates pancreatic cancer cell growth, invasion and migration though mircroRNA-335-5p/c-met axis.

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