Decreased miR-320 and increased AQP1 in patients with breast cancer and the clinical significance
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Triple-negative breast cancer (TNBC) is a common type of breast malignancy with high a propensity for metastasis and locoregional recurrence. The aim of the present study was to investigate the expression of aquaporin (AQP) 3 and AQP5, analyze their association with clinicopathological parameters and explore their clinical significance in tissue samples from patients with TNBC. Immunohistochemistry was performed to detect the expression patterns of AQP3 and AQP5 in 96 patients with TNBC who underwent surgery between 2007 and 2012. AQP3 and AQP5 were expressed primarily in the membrane and cytoplasm of tumor cells within TNBC tissues. AQP3 and AQP5 expression was notably stronger in carcinoma tissue compared with adjacent normal tissue. Overexpression of AQP3 and AQP5 was significantly associated with tumor size, lymph node status and local relapse/distant metastasis. In addition, aberrant overexpression of AQP5 was observed more frequently in TNBC tissues with higher Ki-67 expression than in those with lower Ki-67 expression. In univariate analysis, patients with TNBC with high AQP3 and AQP5 expression demonstrated poorer 5-year disease-free survival and overall survival compared with patients with low AQP3 and AQP5 expression. In multivariate analysis, the combined expression of AQP3 and AQP5 was an independent prognostic marker in patients with TNBC. The results of the present study suggest that the overexpression of AQP3 and AQP5 may serve as a novel therapeutic marker in patients with TNBC.
Triple-negative breast cancer
Aquaporin 3
Surgical oncology
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Breast cancer is one of the most common tumors for women globally. Various miRNAs have been reported to play a crucial role in breast cancer, however the clinical significance of miR-1908-3p in breast cancer remains unclear. The present study aimed to explore the role of miR-1908-3p in breast cancer.The expression of miR-1908-3p was detected in 50 pairs of breast cancer tissues and adjacent normal tissues, 60 breast cancer patient serum and 60 healthy volunteer serum. The functional roles of miR-1908-3p in breast cancer cells such as proliferation, migration and invasion were evaluated using CCK8, SRB, wound healing and transwell chambers. In addition, bioinformatics tools were used to identify potential targets of miR-1908-3p.The results showed that the expression of miR-1908-3p were increased in breast cancer tissues and serum compared with normal breast tissues and serum of healthy volunteers respectively. Furthermore, the young breast cancer patients and HER2-positive patients had a higher level of tissues' miR-1908-3p than elder breast cancer patients and HER2-negative patients, respectively. The young breast cancer patients had a higher level of serum miR-1908-3p than elder breast cancer patients, ROC analysis suggested that miR-1908-3p had the potential as a promising serum diagnostic biomarker of breast cancer. Up-regulation of miR-1908-3p promoted the cells proliferation, migration and invasion while knockdown of miR-1908-3p inhibited these processes in breast cancer cell MCF-7 and MDA-MB-231. The potential target genes of miR-1908-3p in breast cancer included ID4, LTBP4, GPM6B, RGMA, EFCAB1, ALX4, OSR1 and PPARA. Higher expression of these eight genes correlated with a better prognosis for breast cancer patients.These results suggest that miR-1908-3p may exert its oncogenic functions via suppression of these eight genes in breast cancer.
Surgical oncology
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Breast cancer is the most common female tumor in the world. MicroRNA has been reported to play an important role in the progression of breast cancer. The purpose of this study was to explore the role of miR-937-3p in breast cancer.Expression of miR-937-3p in breast cancer tissues and serums was detected from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and patients' samples. Kaplan-Meier plotter identified the association between miR-937-3p and prognosis.The analysis of TCGA, GEO and qRT-PCR suggested that the level of miR-937-3p was increased in breast cancer tissues and serum compared with adjacent normal breast tissues and healthy persons, respectively. The decreased expression of miR-937-3p inhibited breast cancer proliferation, migration and invasion. CCRL2 was the target of miR-937-3p. In contrast to miR-937-3p, the level of CCRL2 was decreased in breast cancer tissues. Luciferase reporter assay revealed that miR-937-3p directly bound to the 3'-UTR of CCRL2. Double knockdown of CCRL2 and miR-937-3p promoted breast cancer cell proliferation, migration and invasion, suggesting that miR-937-3p promoted breast cancer cell proliferation, migration and invasion by targeting CCRL2. The Kaplan-Meier survival analysis suggested that breast cancer patients with high level of miR-937-3p or low level of CCRL2 had a reduced overall survival (OS).miR-937-3p plays an important role in the diagnosis and prognosis of breast cancer. Inhibition of miR-937-3p expression may be a novel targeted therapy for breast cancer.
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Colorectal cancer is an increasing cause of death. Circulating microRNAs (miRs) could be great diagnostic and prognostic biomarkers of colorectal cancer, but further continuation of their utility is needed for their comprehensive application.Twenty-seven patients with colonic cancer, 16 with rectal cancer and 12 healthy volunteers as controls, were involved in this study. Expression of miR-155, miR-21, miR-221, miR-30a, miR-34a and miR-29a were determined by reverse transcription polymerase chain reaction (RT-PCR) from sera of patients.Expression of miR-155, miR-21 and miR-221 was significantly higher in rectal cancer than in colonic cancer. There was no difference found between those with TNM1 cancer and controls for both cancer types. miR-155, miR-34a and miR-29a were down-regulated in all patients with cancer compared to controls. We did not find any statistically significant up-regulation of miR-221 in patients with colonic cancer compared to controls. In contrast, in patients with rectal cancer, miR-221 expression was higher than in controls. Advanced stage was also linked to higher miR-221 expression compared to early stage. Slight, but statistically significant increase was observed in miR-30a expression in patients with colon cancer compared to control individuals.Our results partly support previous findings. Here we report on differences in the expression of circulating microRNA between colonic and rectal tumours for the first time.
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Abstract 1094: MicroRNA-30a inhibits vimentin expression and as a prognostic marker in breast cancer
Abstract Recent studies have suggested a significant role of microRNAs (miRNAs) in the regulation of cancer development. This study examined whether they play a role in breast cancer progression.A miRNA microarray analysis was performed on laser-capture microdissected breast tumors of different lymph-node metastasis status showing different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify specific miRNAs that exhibit significant differences in expression. Functional interaction between the candidate miRNA (i.e. miR-30a) and the gene (i.e. Vim gene, coding for vimentin, a protein involved in epithelial-mesenchymal transition) possibly regulated by miR-30a was verified. We further examined whether decreased expression of miR-30a was associated with breast cancer progression.miR-30a negatively regulated vimentin expression, by binding to the 3′-untranslated region of Vim. Ectopic expression of miR-30a was found to suppress the migration and invasiveness phenotypes of breast cancer cell lines. More importantly, breast cancer patients with decreased miR-30a level in primary cancerous sites were found to be associated with poor clinical features (late tumor stage and lymph node metastasis) and worse progression, demonstrating an increased hazard ratio (HR) for recurrence or recurrence plus mortality during the follow-up period (P<0.05). These findings provide a support of clinical importance of miR-30a in mediating breast tumor progression. Identification of miR-30a-mediated regulation of vimentin might provide a promising therapeutic target in treating breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1094. doi:1538-7445.AM2012-1094
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<b><i>Background:</i></b> With the increasing number of cases of breast cancer every year, the exploration of novel biomarkers has drawn attention. miR-331 has been demonstrated to play a role in various cancers, but its role in breast cancer is still unknown. <b><i>Methods:</i></b> In this study, we included 121 patients with breast cancer treated at Affiliated Hospital of Weifang Medical University. Breast cancer tissues and adjacent normal tissues were collected during the surgery. The expression of miR-331 in breast cancer tissues and cell lines was detected by qRT-PCR assay. Then, with the help of Kaplan-Meier survival and Cox regression analyses, the role of miR-331 in the prognosis of breast cancer was analyzed. Finally, the effect of miR-331 on cell proliferation, migration, and invasion was investigated with CCK-8 assay and transwell assay. <b><i>Results:</i></b> miR-331 was significantly upregulated in breast cancer tissues compared with normal tissues. The overexpression of miR-331 was associated with lymph node metastasis, TNM stage, and poor prognosis. From the results of Cox regression analyses, it was found that miR-331 served as an independent indicator in the prognosis of breast cancer. In addition, miR-331 was also found to be upregulated in breast cancer cells, which promoted cell proliferation, migration, and invasion of breast cancer. <b><i>Conclusion:</i></b> As shown from our data, miR-331 may be a potential prognostic biomarker in breast cancer. Moreover, the development and progression of breast cancer may involve miR-331. These findings suggest a novel therapeutic target for the treatment of breast cancer.
CA 15-3
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Aquaporins (AQPs), also called water channels, have been shown to have functions in the migration, invasion, and proliferation of human breast tumor cells. Most AQP mRNA expression levels were tested by cell lines, mouse models, and even human breast tissues. However, the mRNA expression of individual AQPs in different clinicopathologic characteristics and prognostic values according to different kinds of classifications of breast cancer patients remains unclear.In the current study, we used the Oncomine database, Breast cancer Gene-Expression Miner v4.1, Kaplan-Meier Plotter, and cBioPortal to investigate the expression distribution and prognostic values of AQPs in breast cancer patients.Our study revealed that the mRNA expression levels of AQP8, AQP9, and AQP10 were upregulated, while those of AQP3, AQP4, AQP5, and AQP7 were downregulated in breast cancer. The clinical database showed that lower mRNA levels of AQP1 were associated with a high Scarff-Bloom-Richardson grade, but AQP9 showed the opposite trend. Further survival analyses indicated that high mRNA expression levels of AQP0, AQP1, AQP2, AQP4, AQP6, AQP8, AQP10, and AQP11 were significantly associated with better relapse-free survival (RFS). Conversely, AQP3 and AQP9 were associated with worse RFS in breast cancer patients, suggesting that these two genes might be potential targets in future chemotherapy.These significant AQP members might be further explored as new biomarkers for breast cancer prognosis, but this needs further study.
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Abstract Endometrial cancer (EC) is the leading malignant tumor occurring in the female genital tract and some subtypes are highly invasive and metastatic. miRNAs are small non-coding RNAs that have a broad impact on cancer progression. In particular, miR-194 regulates epithelial to mesenchymal transition (EMT) by suppressing the expression of BMI-1 in EC. In this retrospective study, the clinical significance of miR-194 was investigated in archival EC specimens. We extracted total RNA from thirty-two EC samples and quantified the expression level of miR-194. We discovered that the expression level of miR-194 was significantly (P = 0.03) lower in type I EC patients with more advanced stage. In addition, patients with higher miR-194 levels have better prognosis than those with lower miR-194 levels (P = 0.0067; Cut-off value of miR-194 = 0.3). These results indicate that miR-194 has potential to serve as prognostic biomarker for EC patients. Citation Format: Haiyan Zhai, Mihriban Karaayvaz, Peixin Dong, Noriaki Sakuragi, Jingfang Ju. Prognostic significance of miR-194 in endometrial cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5293. doi:10.1158/1538-7445.AM2013-5293
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Dysregulated miR-125 observed in multiple cancer types has suggested that it is involved in malignant proliferation and invasion. However, the clinical significance of miR-125 in human breast cancer (BC) has not yet been fully elucidated. In the present study, the expression of miR-125a-5p/3p and miR-125b in 143 pairs of BC and normal adjacent tissues (NATs) was measured by real-time quantitative PCR, and the correlation between expression and clinicopathological features was explored. miR-125a-5p and miR-125b were significantly down-regulated in BC tissue samples compared with their matched NAT samples, while the difference in miR-125a-3p expression between BC tissues and NATs was not statistically significant. The expression level of miR-125a-5p was found to be significantly higher in younger patients (<35 years) than in older patients (≥35, P = 0.005). When the patients were divided into three groups according to age (<35, 36-48, and ≥48 years), a gradual reduction in miR-125a-5p expression was observed in BC tissue samples that correlated to increases in age (P = 0.009). There were no significant correlations between miR-125 expression and other clinicopathological features including tumor size, histological grade, hormone receptor status, Her-2 status, and lymph node metastasis. Taken together, these findings suggest that miR-125a-5p may play an important role in BC progression in an age-dependent manner, and that the down-regulation of miR-125a-5p and miR-125b may serve as independent predictors for breast cancer.
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The relationship between microRNAs, such as miR-654-5p and miR-376b-3p, and the prognosis of colon cancer has not been studied until now.To evaluate the expression levels of miR-654-5p and miR-376b-3p and their clinical significance in colon cancer.RT-qPCR was performed to evaluate miR-654-5p and miR-376b-3p expression in 34 pairs of colon cancer and adjacent noncancerous tissues. Subsequently, the association of miR-654-5p and miR-376b-3p expression with clinical factors or the survival of patients suffering from colon cancer was determined by using The Cancer Genome Atlas.miR-654-5p was upregulated and miR-376b-3p was downregulated in colon cancer tissues compared with adjacent noncancerous tissues (P < 0.001). Increased miR-654-5p and decreased miR-376b-3p expression levels were significantly associated with metastasis and clinical stage. Moreover, a univariate analysis demonstrated that colon cancer patients with high miR-654-5p or low miR-376b-3p expression (P = 0.044 and 0.007, respectively) had a poor overall survival rate. A multivariate analysis identified high miR-654-5p expression and low miR-376b-3p expression as independent predictors of poor survival in colon cancer patients.Upregulated miR-654-5p and downregulated miR-376b-3p may be associated with tumour progression in colon cancer, and these microRNAs may serve as independent prognostic markers for colon cancer.
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