miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

Hu, Yingbin; Tang, Ziyuan; Jiang, Bingyan; Chen, Juying; Fu, Zhongpin

doi:10.3892/ol.2017.5673

Cited by 30 publications

(26 citation statements)

References 28 publications

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“… 7 Moreover, the significance of miRNAs in breast cancer has been documented by a study. 8 For example, miR-198 inhibited cell proliferation and migration and promoted cell adhesion in aggressive breast cancer by targeting CUB domain-containing protein 1 (CDCP1); 9 miR-340 suppressed the migration, invasion, and metastasis of breast cancer cells through modulating Wnt/β-catenin signaling pathway; 10 miR-148a accelerated cell apoptosis and restricted growth of breast cancer cells via regulating B-cell lymphoma 2 (Bcl-2). 11 Therefore, miRNAs are regarded as reliable prognostic markers, promising therapeutic targets, or new drugs, which would be essential in the prevention and treatment of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

Dong¹,

Cheng²,

Liu³

et al. 2017

OTT

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Breast cancer remains a major cause of cancer-related death in women worldwide. Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of breast cancer. Moreover, it was found that GIT1 was widely involved in the development of many human cancers. Herein, we aimed to investigate the expression changes of miR-149* and GIT1 and the functional effects of miR-149*/GIT1 link in breast cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to examine the expression levels of miR-149* and GIT1. Dual luciferase reporter assay was utilized to confirm the target interaction between miR-149* and GIT1. The biological functions, including cell proliferation, invasion, and migration, of miR-149* and GIT1 were determined by MTT assay and Transwell assays, respectively. Eventually, the tumor xenograft model in nude mice injected with stable transfected MDA-MB-231 cells was established to verify the effects of miR-149* and GIT1 on tumor growth. Our results showed that miR-149* expression was decreased, whereas GIT1 expression was increased in clinical samples of breast cancer. Based on the inverse expression trend between miR-149* and GIT1, we further demonstrated that miR-149* indeed directly targets GIT1. Subsequently, it was observed that inhibition of miR-149* significantly promoted cell proliferation, invasion, and migration, but the ability of cell proliferation, invasion, and migration was obviously declined after silencing of GIT1 in MDA-MB-231 cells transfected with miR-149* mimic and/or si-GIT1. Finally, it was also found that elevated miR-149* decelerated the tumor growth, while restored GIT1 accelerated the tumor growth in nude mice after 35 days of tumor xenograft. Collectively, these findings concluded that miR-149* might exert a tumor suppressive role in breast cancer by targeting GIT1.

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Section: Introductionmentioning

confidence: 99%

Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

Dong¹,

Cheng²,

Liu³

et al. 2017

OTT

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show abstract

“…miRNAs participate in the modulation of greater than one-third of human genes (10). Studies have indicated that miRNAs are dysregulated in various types of human cancers, such as gastric cancer (11), hepatocellular carcinoma (12), bladder cancer (13), ovarian cancer (14) and breast cancer (15). Abnormally expressed miRNAs have been implicated in tumour initiation and progression, and may regulate a variety of important physiological events, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration and invasion and metastasis (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-197 inhibits gastric cancer progression by directly targeting metadherin

Liao

Zhou

et al. 2017

Mol Med Report

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Gastric cancer is the fifth most frequent malignancy and the fourth most common cause of cancer‑associated mortality worldwide. MicroRNAs (miRNAs) are a group of small RNAs that regulate several cellular processes. In particular, a large number of miRNAs are involved in gastric cancer formation and progression. Thus, miRNAs may be considered as effective diagnostic biomarkers and therapeutic methods for gastric cancer. The aim of the current study was to detect miRNA (miR)‑197 expression in gastric cancer and to investigate its biological role and associated mechanism in gastric cancer. In the present study, miR‑197 expression was demonstrated to be considerably downregulated in gastric cancer tissues and cell lines. Its low expression level was associated with tumour size, invasive depth, tumour‑node‑metastasis staging and lymph node metastasis. High expression of miR‑197 inhibited tumour cell proliferation and invasion in vitro. Subsequently, metadherin (MTDH) was identified as a direct target gene of miR‑197 in gastric cancer, and this was confirmed by bioinformatics analysis, Dual‑luciferase reporter assay, reverse transcription quantitative polymerase chain reaction and western blot analysis. MTDH expression was upregulated in gastric cancer and was inversely correlated with miR‑197 expression levels. In addition, MTDH overexpression prevented the proliferation and inhibited invasion induced by miR‑197 overexpression. In addition, miR‑197 was demonstrated to regulate the phosphatase and tensin homolog (PTEN)/AKT signalling pathway in gastric cancer. The results of the present study suggested that miR‑197 serves a tumour‑suppressing role in human gastric carcinogenesis and progression by regulating the MTDH/PTEN/AKT signalling pathway. The miR‑197/MTDH axis may provide a novel effective therapeutic target for patients with gastric cancer.

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“…MiR-198-5p has been reported to be upregulated in multiple myeloma [ 14 ], chronic pancreatitis or pancreatic ductal adenocarcinoma [ 15 ], Parkinson’s disease [ 16 ], esophageal cancer [ 17 ], preeclampsia [ 18 ], pancreatic adenocarcinoma, ampullary adenocarcinoma [ 19 ], lupus nephritis [ 20 ], retinoblastoma [ 21 ], anencephaly [ 22 ], and squamous cell carcinoma of tongue [ 23 ]. On the other hand, low expression of miR-198-5p has been found in prostate cancer [ 24 ], breast cancer [ 25 ], glioblastoma [ 26 , 27 ], hepatocellular carcinoma [ 28 ], especially hepatitis C virus-associated hepatocellular carcinoma [ 29 , 30 ], osteosarcoma [ 31 ], gastric cancer [ 32 ], colorectal cancer [ 33 ], pancreatic cancer [ 34 ], and respiratory syncytial virus (RSV) infection [ 35 ]. The overexpression of miR-198-5p has also been documented in CD8+ T cells in renal cell carcinoma [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…In hepatocellular carcinoma, miR-198-5p has been shown to target the HGF/c-MET pathway [ 38 ]. Several studies have revealed that the expression of miR-198-5p is greatly related to lymph node metastasis or distant metastasis in different malignant diseases, such as breast cancer [ 25 ], osteosarcoma [ 31 ], gastric cancer [ 32 ], and colorectal cancer [ 33 ]. Some studies have also shown that miR-198-5p is closely related to cell proliferation, apoptosis, and migration [ 12 , 14 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR

et al. 2018

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BackgroundTo examine the clinical value of miR-198-5p in lung squamous cell carcinoma (LUSC).MethodsGene Expression Omnibus (GEO) microarray datasets were used to explore the miR-198-5p expression and its diagnostic value in LUSC. Real-time reverse transcription quantitative polymerase chain reaction was used to evaluate the expression of miR-198-5p in 23 formalin-fixed, paraffin-embedded (FFPE) LUSC tissues and corresponding non-cancerous tissues. The correlation between miR-198-5p expression and clinic pathological features was assessed. Meanwhile, putative target messenger RNAs of miR-198-5p were identified based on the analysis of differentially expressed genes in the Cancer Genome Atlas (TCGA) and 12 miRNA prediction tools. Subsequently, the putative target genes were sent to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses.ResultsMiR-198-5p was low expressed in LUSC tissues. The combined standard mean difference (SMD) values of miR-198-5p expression based on GEO datasets were − 0.30 (95% confidence interval (CI) − 0.54, − 0.06) and − 0.39 (95% CI − 0.83, 0.05) using fixed effect model and random effect model, respectively. The sensitivity and specificity were not sufficiently high, as the area under the curve (AUC) was 0.7749 (Q* = 0.7143) based on summarized receiver operating characteristic (SROC) curves constructed using GEO datasets. Based on the in-house RT-qPCR, miR-198-5p expression was 4.3826 ± 1.7660 in LUSC tissues and 4.4522 ± 1.8263 in adjacent normal tissues (P = 0.885). The expression of miR-198-5p was significantly higher in patients with early TNM stages (I-II) than that in cases with advanced TNM stages (III-IV) (5.4400 ± 1.5277 vs 3.5690 ± 1.5228, P = 0.008). Continuous variable-based meta-analysis of GEO and PCR data displayed the SMD values of − 0.26 (95% CI − 0.48, − 0.04) and − 0.34 (95% CI − 0.71, 0.04) based on fixed and random effect models, respectively. As for the diagnostic value of miR-198-5p, the AUC based on the SROC curve using GEO and PCR data was 0.7351 (Q* = 0.6812). In total, 542 genes were identified as the targets of miR-198-5p. The most enriched Gene Ontology terms were epidermis development among biological processes, cell junction among cellular components, and protein dimerization activity among molecule functions. The pathway of non-small cell lung cancer was the most significant pathway identified using Kyoto Encyclopedia of Genes and Genomes analysis.ConclusionThe expression of miR-198-5p is related to the TNM stage. Thus, miR-198-5p might play an important role via its target genes in LUSC.

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miR-198 functions as a tumor suppressor in breast cancer by targeting CUB domain-containing protein 1

Cited by 30 publications

References 28 publications

Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

MicroRNA-197 inhibits gastric cancer progression by directly targeting metadherin

Clinical value of miR-198-5p in lung squamous cell carcinoma assessed using microarray and RT-qPCR

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