Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues from Chinese patients with gastric cancer

Liu, Li; Chen, Qi; Lai, Renchun; Wu, Xiaobin; Wu, Xiaoyu; Liu, Fei; Xu, Guohua; Ji, Yong

doi:10.1016/s1674-8301(10)60028-0

Cited by 23 publications

(18 citation statements)

References 53 publications

(58 reference statements)

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“…In previous studies, miR-155 was overexpressed in cancer tissues of 91 patients by formalin-fixed paraffin-embedded (FFPE) (34), and related to tumor penetration through serosa and lymph node metastasis (35). However, there is also a study on miR-155 significantly downregulated in gastric cancer cell lines compared with GES-1, and overexpression of miR-155 significantly reduced the protein levels of SMAD2 (36).…”

Section: Discussionmentioning

confidence: 99%

The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis

Xie

Liu

et al. 2014

International Journal of Oncology

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Slit-Robo GTPase-activating protein 1 (SRGAP1) functions as a GAP for Rho-family GTPases and downstream of Slit-Robo signaling. We aim to investigate the biological function of SRGAP1 and reveal its regulation by deregulated microRNAs (miRNAs) in gastric cancer (GC). mRNA and protein expression of SRGAP1 were examined by quantitative reverse transcription PCR (qRT-PCR) and western blot. The biological role of SRGAP1 was demonstrated through siRNA-mediated knockdown experiments. The regulation of SRGAP1 by miR-340 and miR-124 was confirmed by western blot, dual luciferase activity assays and rescue experiments. SRGAP1 is overexpressed in 9 out of 12 (75.0%) GC cell lines. In primary GC samples from TCGA cohort, SRGAP1 shows gene amplification in 5/258 (1.9%) of cases and its mRNA expression demonstrates a positive correlation with copy number gain. Knockdown of SRGAP1 in GC cells suppressed cell proliferation, reduced colony formation, and significantly inhibited cell invasion and migration. Luciferase reporter assays revealed that SRGAP1 knockdown significantly inhibited Wnt/β-catenin pathway. In addition, SRGAP1 was found to be a direct target of two tumor-suppressive miRNAs, miR-340 and miR-124. Concordantly, these two miRNAs were downregulated in primary gastric tumors and these decreasing levels w5ere associated with poor outcomes. Expression of miR-340 and SRGAP1 displayed a reverse relationship in primary samples and re-expressed SRGAP1, rescued the anti-cancer effects of miR-340. Taken together, these data strongly suggest that, apart from gene amplification and mutation, the activation of SRGAP1 in GC is partly due to the downregulation of tumor-suppressive miRNAs, miR-340 and miR-124. Thus SRGAP1 is overexpressed in gastric carcinogenesis and plays an oncogenic role through activating Wnt/β-catenin pathway.

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Section: Discussionmentioning

confidence: 99%

The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis

Xie

Liu

et al. 2014

International Journal of Oncology

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“…Differential expression of miRNAs has been reported for various tumor entities including gastric cancer 7 9 10 . Especially increased expression of miR-21 is identified both in tumor tissues and in blood of GC patients when compared to controls 11 and its oncogenic role has been widely studied 10 12 13 14 . However, the understanding of miRNA deregulation in the stomach related to H.pylori infection and different stages of progression according to Correa's cascade is still preliminary 7 .…”

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confidence: 99%

Differential expression of microRNAs in preneoplastic gastric mucosa

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Schirrmeister

Langner

et al. 2015

Sci Rep

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Gastric carcinogenesis is a multifactorial H.pylori-triggered dynamic process that goes through a cascade of preneoplastic conditions. The expression of miRNAs in the stomach with regard to preneoplastic precursor conditions and H.pylori infection has not been investigated systematically. In this prospective proof-of-principle study, we evaluated the miRNA expression in gastric antrum and corpus mucosa from patients with chronic non-atrophic gastritis (CNAG), atrophic gastritis (AG), and GC compared to controls. Gastric normal mucosa shows a unique expression pattern for miR-21, miR-155 and miR-223, which is specific for different regions. In correlation with progression of Correa's cascade and H.pylori infection, we observed a gradual increase in miR-155 and miR-223 both in corpus and antrum and miR-21 only in the antrum mucosa. Using miRNA expression we calculated a score that allowed us to discriminate patients with AG from subjects with normal mucosa with high diagnostic accuracy in testing and validation cohorts reproducibly. In summary, the expression pattern of miRNAs in the gastric mucosa is gradually increased with progression of Correa's cascade and H.pylori infection, suggesting miRNAs as potential biomarkers for preneoplastic precursor conditions. However, differences of miRNA expression between the gastric antrum and the corpus need to be considered in future studies.

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“…Although miR-145 expression in GC has been discussed by several authors (25)(26)(27)(28), there is no unified view of the altered expression of miR-145 in scirrhous type GC. To confirm miR-145 expression in GC tissue, we performed qRT-PCR in 20 frozen GC tissue samples.…”

Section: Resultsmentioning

confidence: 99%

“…The apparent discrepancy between the data obtained from scirrhous type GC and other malignancies is worth consideration. It should be noted that these previous reports focused on cancer cells or normal stromal cells and not on peri-tumoral fibroblasts (26)(27)(28)(29)(30)(31). We previously found that the expression of miR-143, co-regulated with miR-145, was localized in fibroblasts of scirrhous type GC and was associated with poor prognosis in the patients with GC (13).…”

Section: Discussionmentioning

confidence: 98%

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MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer

et al. 2014

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Abstract. Gastric cancer (GC) is one of the most common malignancies worldwide. In particular, scirrhous type GC is highly metastatic and is characterized clinically by rapid disease progression and poor prognosis. MicroRNAs (miRNAs) play crucial roles in cancer development and progression. We previously demonstrated by microarray analysis that microRNA-145 (miR-145) is one of the more highly expressed miRNAs in scirrhous type GC vs. non-scirrhous types of GC. In the present study, we investigated the role of miR-145 in scirrhous type GC. The expression levels of miR-145 assessed by quantitative RT-PCR were higher in scirrhous type GC tissue samples than in non-scirrhous type GC and corresponding normal tissues. GC patients with high miR-145 expression were at a more advanced tumor stage (P=0.0156) and had more scirrhous type histology (P=0.0054) than those with low miR-145 expression. Furthermore, miR-145 expression was significantly associated with poor prognosis in GC patients (P=0.0438). miR-145 expression was localized in stromal fibroblasts of scirrhous type GC but not in cancer cells. miR-145 was induced by treatment by transforming growth factor-β, and it enhanced the expression of α-smooth muscle actin, a marker of myofibroblasts, in both normal gastric fibroblasts and cancer-associated fibroblasts. These data suggest that miR-145 may contribute to the progression of scirrhous type GC by regulating activation of peri-tumoral fibroblasts.

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Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues from Chinese patients with gastric cancer

Cited by 23 publications

References 53 publications

The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis

The clinical significance of downregulation of mir-124-3p, mir-146a-5p, mir-155-5p and mir-335-5p in gastric cancer tumorigenesis

Differential expression of microRNAs in preneoplastic gastric mucosa

MicroRNA-145 is a potential prognostic factor of scirrhous type gastric cancer

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