Survival prediction of gastric cancer by a seven-microRNA signature

Li, X.; Zhang, Y.; Ding, Jie; Wu, Kaichun; Fan, Daiming

doi:10.1136/gut.2008.175497

Cited by 292 publications

(228 citation statements)

References 21 publications

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“…Previous studies have demonstrated that miR-30a is involved in the progression of various malignant tumors (20,21,23). However, the mechanism of miR-30a in the progression of cervical cancer remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Zhao

Shu

et al. 2017

Oncol Lett

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Abstract. Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells. A functional assay using miR-30a mimic demonstrated that miR-30a could inhibit the growth and invasion of cervical cancer cells. Additionally, bioinformatics-based prediction and luciferase reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection with miR-30a reduced the mRNA expression and protein levels of MEF2D, as determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression was negatively correlated with that of miR-30a in cervical cancers. Overall, the present study demonstrated that miR-30a functions as a tumor suppressor by targeting MEF2D in cervical cancer, which may provide the basis for a prognostic biomarker or therapeutic strategy for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence indicates that the dysregulation of miR-30a contributes to various malignant tumors, including lung, thyroid, gastric, breast and colon cancer (18)(19)(20)(21)(22)(23). miR-30a promotes tumorigenesis in these cancers by directly targeting tumor-associated proteins.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Zhao

Shu

et al. 2017

Oncol Lett

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“…Ueda et al reported the results of miRNA expression profiling in gastric cancer tissues and demonstrated that elevated levels of let-7 and miR-214 are associated with an unfavorable outcome (6). Li et al developed a seven-miRNA signature that functions as an independent predictor for relapse-free and overall survival in patients with gastric cancer (7).…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-17-5p and miR-20a: Molecular markers for gastric cancer

Wang

et al. 2012

Mol Med Report

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Abstract. have been demonstrated to be elevated in the plasma of gastric cancer patients. However, the clinical significance of the circulating levels of these microRNAs (miRNAs), the predictive power for prognosis and application for monitoring of chemotherapeutic effects remain unclear. To this end, we measured plasma miR-17-5p/20a levels in unpaired pre-operative (n=65), post-operative (n=16) and relapse (n=6) gastric cancer patient groups. The 3-year overall survival rate for the unpaired pre-operative patients was recorded. The circulating levels of miR-17-5p/20a were also tested in paired pre-operative and post-operative plasma from 14 gastric cancer patients. We found that the concentrations of miR-17-5p/20a were significantly associated with the differentiation status and TNM stages of gastric cancer. The miRNA levels in the different groups reflected pathological tumor progression. Kaplan-Meier curve analysis revealed that high expression levels of miR-17-5p/20a were significantly correlated with poor overall survival. Cox regression analysis demonstrated that the level of plasma miR-20a was an independent risk predictor for prognosis. An in vivo mouse tumor model was established and antagomirs against miR-17-5p/20a were applied as chemotherapeutics to perform tumor treatment. An assay of serum miR-17-5p/20a levels showed that the levels of serum miRNAs were notably reduced in post-treated mice with tumor volume regression. Taken together, the levels of circulating miR-17-5p/20a may be a promising non-invasive molecular marker for pathological progression, prediction of prognosis and monitoring of chemotherapeutic effects for gastric cancer.

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“…miR-17-5p is part of the miR-17-92 polycistronic cluster, a family of oncogenic miRNAs (miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92-1) commonly deregulated in cancer, on chromosome 13 (16). It was previously reported that miR-17 is upregulated in colorectal (17)(18)(19), gastric (19,20) and pancreatic adenocarcinomas (19). A previous study demonstrated that miR-17-5p directly controls the expression of the type II transforming growth factor-β (TGF-β) receptor in colorectal cancer progression, inhibits the transcription of individual TGF-β responsive genes and indirectly stimulates angiogenesis through inhibition of a wide repertoire of anti-angiogenic factors (21).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of microRNA-17-5p inhibits drug resistance of gastric cancer cells partially through targeting p21

Wang

2018

Oncol Lett

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Abstract. MicroRNAs (miRNAs/miRs) are endogenous small non-coding RNAs that post-transcriptionally regulate the expression of genes and serve crucial roles in diverse biological processes. The present study aimed to examine the miRNA expression profile and drug resistance in the SGC7901 cell line and its isogenic drug-resistant counterpart, SGC7901/cisplatin (DDP) cell line. The potential role of miR-17-5p in modulating drug resistance in gastric cancer cells was investigated. Different levels of miRNA expression between SGC7901/DDP and SGC7901 cells were analyzed by miRNA microarray and validated by quantitative polymerase chain reaction. It was indicated that the downregulation of miR-17-5p sensitized SGC7901/DDP cells to anticancer drugs. A decreased luciferase activity of p21 3'-untranslated region-based reporter in miR-17-5p-transfected SGC7901/DDP cells suggested that p21 may be a direct target gene of miR-17-5p. Western blot analysis and flow cytometric assay revealed that the downregulation of miR-17-5p increases the sensitivity of SGC7901/DDP cells to DDP-induced apoptosis. Taken together, these results demonstrated that miR-17-5p may perform a role in the development of drug resistance in gastric cancer cells, at least partially by modulating apoptosis via targeting p21. IntroductionGastric cancer is one of the major causes of mortality worldwide (1). Currently, the standard treatment regimen for gastric cancer includes surgery, chemotherapy and radiotherapy (2). In patients at advanced stages, chemotherapy has been demonstrated to improve survival, by preventing tumor invasion or downsizing distant metastatic lesions (3). One of the leading causes of chemotherapy failure in gastric cancer is tumor resistance. Patients who are less responsive to chemotherapy have a poorer prognosis (4). Thus, it is important to identify the molecular mechanisms underlying the drug resistance of gastric cancer cells.MicroRNAs (miRNAs/miRs) are a family of endogenous non-coding RNA molecules that can post-transcriptionally regulate gene expression and have been shown to perform crucial roles in diverse biological processes, including apoptosis, proliferation, stress response and metabolism (5). miRNAs have been revealed to be associated with cell chemosensitivity or chemotherapy resistance in a variety of cancer cell types, including ovarian and breast cancer cells (6-8). However, there is limited available data on the potential role of miRNAs in the chemotherapy resistance of gastric cancer.The present study reported that miR-17-5p was upregulated in the multidrug-resistant human gastric cancer SGC7901/cisplatin (DDP) cell line, compared with the parental SGC7901 cell line. It was demonstrated that the downregulation of miR-17-5p was able to inhibit drug resistance and increase DDP-induced apoptosis. In addition, it was indicated that p21 was upregulated in miR-17-5p-transfected cells compared with cells transfected with control miRNA inhibitor. These results demonstrated that miR-17-5p may perform a role in the develop...

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Survival prediction of gastric cancer by a seven-microRNA signature

Abstract: Our seven-miRNA signature is closely associated with relapse-free and overall survival among patients with gastric cancer. The prognostic signature could be applicable to future decisions concerning treatment.

Cited by 292 publications

References 21 publications

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Downregulation of miR‑30a is associated with proliferation and invasion via targeting MEF2D in cervical cancer

Circulating miR-17-5p and miR-20a: Molecular markers for gastric cancer

Downregulation of microRNA-17-5p inhibits drug resistance of gastric cancer cells partially through targeting p21

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