Breast Cancer Metastasis Suppressor 1 Regulates Hepatocellular Carcinoma Cell Apoptosis via Suppressing Osteopontin Expression

Wu, Yanhua; Jiang, Wenjun; Wang, Ying‐Ming; Wu, Jun; Saiyin, Hexige; Qiao, Xuguang; Mei, Xinyu; Guo, Bin; Xiao, Fang; Zhang, Lu; Lou, Huiling; Wu, Chaoqun; Qiao, Shan

doi:10.1371/journal.pone.0042976

Cited by 30 publications

(22 citation statements)

References 61 publications

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“…Low expression of the metastasis suppressor BRMS1 was recently shown to be an independent prognostic factor for poor prognosis both for metastasis-free survival and overall survival in nasopharyngeal carcinoma patients [34]. In a recent study, Wu et al found that the expression level of BRMS1 was significantly down-regulated in hepatocellular carcinoma (HCC) tissues and that BRMS1 sensitizes HCC cells to apoptosis [35]. …”

Section: Discussionmentioning

confidence: 99%

Breast Cancer Metastasis Suppressor-1 Promoter Methylation in Primary Breast Tumors and Corresponding Circulating Tumor Cells

Chimonidou

Kallergi

Georgoulias

et al. 2013

Molecular Cancer Research

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Breast Cancer Metastasis Suppressor-1 differentially regulates expression of multiple genes, leading to metastasis suppression without affecting orthotopic tumor growth. We evaluated BRMS1 promoter methylation as prognostic biomarker in primary breast tumors and studied BRMS1 promoter methylation in a subset of corresponding Circulating Tumor Cells (CTC) for the first time. We analyzed 118 formalin-fixed paraffin embedded samples: 5 pairs of breast tumors and adjacent non-cancerous tissues, 14 non-cancerous tissues, 10 benign fibroadenomas, and 84 primary breast tumors. Peripheral blood mononuclear cells from 39/84 of these patients were fixed in cytospins. BRMS1 methylation status was investigated in all FFPE and cytospin stained CTC using methylation specific PCR. BRMS1 expression in cytospins was examined by double-immunofluorescence using anti-BRMS1 and pancytokeratin A45-B/B3 antibodies. BRMS1 promoter methylation was not observed in noncancerous breast tissues (0%), and benign fibroadenomas (0%), while it was observed in 36.9% of primary breast tumors. BRMS1 promoter methylation in primary tumors was associated with reduced disease-free interval (P=0.009) while a trend towards a reduced overall survival was also observed (P=0.071). 13/39 cytospin samples (33.3%) were positive for the presence of CTC and the total number of the detected CTC was 41. Most CTC (80.5%) were negative for BRMS1 or maintained low expression, implying that BRMS1 is down regulated in these cells. BRMS1 promoter methylation was observed in 5/39 (12.8%) samples. BRMS1 promoter methylation in primary breast tumors provides prognostic information for DFS. BRMS1 expression in CTC was highly heterogeneous, between patients and even in the same patient.

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Section: Discussionmentioning

confidence: 99%

Breast Cancer Metastasis Suppressor-1 Promoter Methylation in Primary Breast Tumors and Corresponding Circulating Tumor Cells

Chimonidou

Kallergi

Georgoulias

et al. 2013

Molecular Cancer Research

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“…It is therefore possible that PAEP promotes tumor cell growth at least in part by downregulating TSP-1 expression. The presence of SPP-1, a putative tumor oncogene (30)(31)(32), in the medium was lost following the knockdown of PAEP. Thus, secretion of SPP-1 is directly related to the presence of PAEP.…”

Section: Discussionmentioning

confidence: 99%

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Chai¹,

Qiao²,

Wang³

et al. 2013

Molecular Medicine Reports

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Abstract. Progestagen-associated endometrial protein (PAEP), also termed glycodelin, is a 28-kDa glycoprotein of the lipocalin superfamily that is expressed in a variety of tumors, including gynecological tumors, lung cancer and melanoma. To determine the biological functions of the PAEP gene in tumor development and progression, the production of transient and stable PAEP knockdown cell models is required. In the present study, RNA interference technology was used to silence PAEP gene expression in melanoma and transfection was screened for and the conditions were optimized using fluorescence microscopy, flow cytometry, qPCR and western blot analysis. The results of the present study showed that the transient transfection of melanoma cells with 100 nmol/l PAEP siRNA or lentiviral PAEP small hairpin RNA (shRNA) [multiplicity of infection (MOI), 100 pfu/cell] efficiently knocked down target gene expression. To establish stable PAEP knockdown cell lines, melanoma cells were infected with a low MOI (10 pfu/cell) of lentiviral particles expressing PAEP shRNA. Following puromycin screening, the PAEP gene knockdown efficiency was demonstrated to be >80% in 624-Mel and 624.38-Mel cell lines, which was validated by western blot analysis. Therefore, melanoma cell lines with stable knockdown of PAEP were successfully established and may be used as effective cell models to study the biological functions of the PAEP gene in melanoma.

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“…The human miR-125a-5p plasmids, miR-control plasmids, anti-miR-125a-5p and anti-miR-control were designed and generated by Shanghai GenePharma Co., Ltd., Shanghai, China (Shanghai, China). The siR NA small-inter fering (si)R NA (#S1 sequence, 5'-GGAAUAAGUACGGAAUGUGA-3') that targets the BRMS1 gene was synthesized by Guangzhou RiboBio Co., Ltd., (Guangzhou, China) as previously described (25). Additionally, the coding sequences [without the 5'-untranslated region (UTR) of BRMS1] was amplified by PCR and cloned into the pcDNA3.1 (+) vector (Shanghai GenePharma Co., Ltd).…”

Section: Rna Extraction and Reverse Transcription-quantitative Polymementioning

confidence: 99%

MicroRNA‑125a‑5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression

Cao

Tan

et al. 2018

Oncol Lett

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Abstract. Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0.01) and normal gastric mucosa cell lines (P<0.01), respectively. Moreover, clinical pathological characteristics and Kaplan-Meier analysis indicated that a low expression of miR-125a-5p was not only associated with lymph metastasis, peritoneal dissemination and advanced tumor-node metastasis stage but also affected the prognosis of GC patients. Compared with miR-control-transfected GC cells, markedly decreased migration and invasion was observed in GC cells that overexpress miR-125a-5p. By contrast, increased metastasis and invasion were observed in miR-125a-5p-knocked down cells compared with the control. Furthermore, luciferase reporter assays indicated that breast cancer metastasis suppressor 1 (BRMS1) was a direct target of miR-125a-5p. Notably, a positive correlation between the levels of BRMS1 and miR-125a-5p in GC tissues was observed, and BRMS1 expression was indicated to be regulated by miR-125a-5p in GC cells. In conclusion, miR-125a-5p may act as a tumor suppressor by targeting the metastasis-inhibitory gene, BRMS1. The data suggesting that BRMS1 is a potential target gene of miR-125a-5p, may provide novel insight into miRNA regulation of human gene expression, and a useful target for gene therapy of GC.

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Breast Cancer Metastasis Suppressor 1 Regulates Hepatocellular Carcinoma Cell Apoptosis via Suppressing Osteopontin Expression

Cited by 30 publications

References 61 publications

Breast Cancer Metastasis Suppressor-1 Promoter Methylation in Primary Breast Tumors and Corresponding Circulating Tumor Cells

Breast Cancer Metastasis Suppressor-1 Promoter Methylation in Primary Breast Tumors and Corresponding Circulating Tumor Cells

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

MicroRNA‑125a‑5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression

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