MiR-3194-3p Inhibits Breast Cancer Progression by Targeting Aquaporin1.

Increasing evidence indicates that the Aquaporin1 (AQP1) aberrant expression may be related to a wide variety of human cancers, including breast cancer (BC). In the present study, we explore the effects and possible mechanism of miR-3194-3p on the biological behaviors of BC. At first, miR-3194-3p is found to modulate AQP1 expression targeting the 3'-UTR using miRNA target prediction algorithms. MiR-3194-3p expression is markedly downregulated, and AQP1 expression is upregulated in BC tissues compared with adjacent normal breast tissues. Moreover, the differential expression of miR-3194-3p and AQP1 are observed in four BC cells with different malignancy degree. Meanwhile, a significant negative correlation between AQP1 and miR-3194-3p expressions in tumor tissues from 30 BC patients is revealed. miR-3194-3p mimic remarkably inhibits cell proliferation, migration, and invasion as well as promotes apoptosis in MDA-MB-231 cells while miR-3194-3p inhibitors exert an opposite role in MCF-7 cells. Dual-luciferase reporter system demonstrates that AQP1 is a direct target gene of miR-3194-3p. Overexpression of AQP1 by pBABE-puro-AQP1 vector partially abrogates the effect of miR-3194-3p mimic in MDA-MB-231 cells. In short, our results suggest that miR-3194-3p suppresses BC cell proliferation, migration, and invasion by targeting AQP1, providing a novel insight into BC tumorigenesis and treatment.

Decreased expression of aquaporin 1 correlates with clinicopathological features of patients with cervical cancer.

Purpose: We aimed to investigate the expression dynamics of Aquaporin 1 (AQP1) in cervical cancer and evaluate correlations among AQP1 levels and the clinicopathological features of patients with cervical cancer. Patients and methods: AQP1 mRNA and protein levels in cervical cancer and adjacent normal tissues were evaluated by quantitative reverse-transcription PCR (qRT-PCR) and western blot. Immunohistochemistry (IHC) for AQP1 was performed with a tissue microarray of cervical cancer (containing 63 cases of squamous cell cervical cancers and 10 normal cervical tissues) to investigate clinicopathological outcomes. Cut-off scores for positive expression of AQP1 were determined by receiver operating characteristic analysis. The χ 2 test was used to analyze correlations among AQP1 expression and clinicopathological features of cervical cancer. Results: The expression of AQP1 was decreased in the majority of cervical cancer tissues by qRT-PCR and western blot analysis. Positive expression of AQP1 was observed in 100% (10/10) of normal cervical tissues and in 42.86% (27/63) of cervical cancer tissues by IHC analysis. The cut-off score for positive expression of AQP1 was determined to be 45% of cancer cells. Decreased expression of AQP1 was correlated with clinicopathological features including; poor pathological grade (P=0.000), late International Federation of Gynecology and Obstetrics stage (P=0.008), and positive lymph nodes (P=0.002). Conclusion: These data suggest that decreased expression of AQP1 correlated with progressive features in patients with cervical cancer. AQP1 levels may serve as a potential biomarker for the diagnosis of cervical cancer.

Decreased expression of Sushi Domain Containing 2 correlates to progressive features in patients with hepatocellular carcinoma.

BACKGROUND: Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. Increasing evidence suggests that SUSD2 plays a key role in tumorigenesis. However, the SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. In the present study, we intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. Furthermore,we examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721. METHODS: We evaluated the SUSD2 expression in HCC tissues and paired normal liver tissues by quantitative real-time PCR and western blotting analysis. The clinicopathological significance of SUSD2 was investigated by immunohistochemistry (IHC) on a HCC tissue microarray. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of SUSD2. The correlation between SUSD2 protein expression and clinicopathological features of HCC was analyzed by Chi square test. The cell proliferation, apoptosis, invasion and migration potential were observed to detect the functions of SUSD2 in HCC cells. RESULTS: Decreased expression of SUSD2 mRNA and protein were observed in the majority of HCC tissues, compared with paired normal liver tissues. When SUSD2 high expression percentage was determined to be above 52.5 % (area under ROC curve = 0.769, P = 0.000), low expression of SUSD2 was observed in 62.2 % (112/180) of HCC tissues and high expression of SUSD2 was observed in all normal liver tissues (16/16) by IHC. Decreased expression of SUSD2 in patients was correlated with high histological grade (χ(2) = 5.198, P = 0.023), advanced clinical stage (χ(2) = 30.244, P = 0.000), pT status (χ(2) = 33.175, P = 0.000), pN status (χ(2) = 4.785, P = 0.029), pM status (χ(2) = 4.620, P = 0.032). Down-regulation of SUSD2 promoted cell proliferation,invasion and migration,reduced the cell apoptosis. CONCLUSIONS: Our findings suggest that SUSD2 may play as a tumor suppressor in HCC cells and could be served as an additional potential marker for diagnosis.

MiR-204-5p/Six1 feedback loop promotes epithelial-mesenchymal transition in breast cancer.

Epithelial-mesenchymal transition (EMT) is a vital process in epithelial cancer invasion and metastasis. The induction of EMT by Six1 has been described as a common mode of cancer progression, which could promote breast cancer migration and invasion. In the study, we found that miR-204-5p could suppress the migration and invasion of breast cancer cell lines. Since overexpression of Six1 promote EMT, we identified a mechanism by which miR-204-5p inhibited the EMT by downregulating the Six1, which was mediated by a conserved miR-204-5p seed-matching sequence in the 3'-UTR of Six1 mRNA. We also identified that upregulation of Six1 could downregulate miR-204-5p expression, affecting the migration and invasion of breast cancer cell lines. In conclusion, the frequent upregulation of Six1 and/or downregulation of miR-204-5p in breast cancer may shift the equilibrium of these reciprocal regulations and lock breast cancer cells in the mesenchymal state.

[RNA interference of HERC4 inhibits proliferation, apoptosis and migration of cervical cancer Hela cells].

OBJECTIVE: To explore the effects of silencing HERC4 on the proliferation, apoptosis, and migration of cervical cancer cell line Hela and the possible molecular mechanisms. METHODS: Three HERC4-specific small interfering RNAs (siRNAs) were transfected into Hela cells, and HERC4 expression in the cells was examined with Western blotting. CCK-8 assay, annexin V-FITC/PI assay, and wound healing assay were used to assess the effect of HERC4 silencing on the proliferation, apoptosis and migration ability of Hela cells. The expression levels of cyclin D1 and Bcl-2 in the cells were detected using Western blotting. RESULTS: Transfection of siRNA-3 resulted in significantly decreased HERC4 protein expression (P<0.01). HERC4 silencing by siRNA-3 markedly suppressed the proliferation and migration of Hela cells, increased the apoptosis rate (P<0.01) and reduced the expression levels of cyclin D1 and Bcl-2 (P<0.01). CONCLUSION: Silencing of HERC4 efficiently inhibits the proliferation, migration, and invasion of Hela cells in vitro, and the underlying mechanisms may involve the down-regulation of cyclin D1 and Bcl-2.

Association between hepatitis B virus infection and diabetes mellitus: A meta-analysis.

Hepatitis B virus (HBV) infection has been shown by certain studies to be associated with diabetes mellitus (DM); however, the results of these studies were controversial. For that reason, a meta-analysis of the literature was performed in order to determine the association between HBV infection and the prevalence of DM more accurately. The PubMed, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases, as well as the Chinese Science and Technology Journal Database, were searched for literature published until June 2014. The reference lists of all relevant articles were also searched. The summary odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were calculated based on a random-effects model. Heterogeneity was assessed using the I2 statistic. Subgroup analyses were conducted based on study type and region for the purpose of assessing the factors that could potentially affect the outcome. A total of 15 eligible studies (in 14 articles) were selected for the meta-analysis, involving 12,974,690 HBV-infected patients and 231,776,232 controls. The OR for the prevalence of DM was 1.33 (95% CI, 1.09-1.62; P=0.005) between the patients with HBV infection and the controls. The subgroup analysis based on study type revealed a significantly higher prevalence of DM in the HBV-infected group than that in the control group in both case-control (OR, 1.89; 95% CI, 1.08-3.30; P=0.025) and cross-sectional (OR, 1.41; 95% CI, 1.04-1.90; P=0.027) studies. The subgroup analysis based on region revealed a significantly higher prevalence of DM in the HBV-infected group than in the control group in the Asia-Pacific region (OR, 1.67; 95% CI, 1.08-2.58; P=0.022). Compared with uninfected patients, the pooled results suggest that HBV-infected patients have a higher risk of developing DM; however, given the fact that this is a meta-analysis of observational studies, further randomized controlled trials are required in order to reach a more accurate conclusion.

Increased expression of Six1 correlates with progression and prognosis of prostate cancer.

Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopathological characteristics in prostate cancer were unclear. In this study, the mRNA and protein levels of Six1 in prostate cancer tissues and normal prostate tissues were evaluated. The clinicopathological significance of Six1 was investigated by immunohistochemistry (IHC) on a prostate cancer tissue microarray. The cut-off score for high expression of Six1 was determined by the receiver-operating characteristic (ROC) analysis. The correlation between Six1 protein expression and clinicopathological characteristics of prostate cancer was analyzed by Chi-square test. Increased expression of Six1 protein was observed in the majority of prostate cancer, compared with their paired adjacent normal prostate tissues. When Six1 high expression percentage was determined to be above 55 % (area under ROC curve = 0.881, P = 0.000), high expression of Six1 was observed in 55.6 % (80/144) of prostate cancer tissues and low expression of Six1 was observed in all normal prostate tissues by IHC. Increased expression of Six1 in patients was correlated with high histological grade (χ2 = 58.651, P = 0.00), advanced clinical stage (χ2 = 57.330, P = 0.000), high Gleason score (χ2 = 63.480, P = 0.000), high primary tumor grade (χ2 = 57.330, P = 0.000) and positive regional lymph node metastasis (χ2 = 19.294, P = 0.000). Furthermore, univariate and multivariate survival analysis suggested that Six1 was an independent prognostic indicator for overall survival (P < 0.05). This study suggests that Six1 could be served as an additional biomarker in identifying prostate cancer patients at risk of tumor progression, might potentially be used for predicting survival outcome of patients with prostate cancer.

Reduced expression of sushi domain containing 2 is associated with progression of non-small cell lung cancer.

Sushi domain containing 2 (SUSD2) has been identified as a gene encoding an 822-amino acid protein, which contains a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies have reported that increased expression of SUSD2 has a critical role in tumorigenesis in human breast cancer. However, to the best of our knowledge, SUSD2 expression status and its correlation with the clinicopathological features of non-small cell lung cancer (NSCLC) have not previously been investigated. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to evaluate SUSD2 messenger RNA (mRNA) and protein expression in NSCLC and adjacent normal lung tissues. The clinicopathological significance of SUSD2 was investigated by immunohistochemical analysis of an NSCLC tissue microarray. Receiver operating characteristic analysis was used to determine the cut-off score for positive expression of SUSD2. Furthermore, the correlation between SUSD2 expression and the clinicopathological features of NSCLC was analyzed by χ2 test. The results revealed that SUSD2 mRNA (P<0.0001) and protein (P<0.0001) expression levels were significantly decreased in NSCLC tissues compared with those of adjacent normal tissues. When the SUSD2 positive expression percentage was determined to be >47.5% (area under ROC curve, 0.799; P<0.000), positive expression of SUSD2 was observed in 100% (32/32) of normal lung tissues and 55% (88/160) of NSCLC tissues by immunohistochemistry (χ2=21.160; P<0.000). Furthermore, it was demonstrated that the reduced SUSD2 protein levels in cancer tissues were positively correlated with poor histological grade (χ2=41.764; P<0.000), advanced clinical stage (χ2=10.790; P=0.013), higher pT (χ2=9.070; P=0.028) and positive regional lymph node metastasis (χ2=15.399; P=0.002). In conclusion, these data suggest that the reduced expression of SUSD2 is associated with the progression of NSCLC and may have a role in the pathogenesis of NSCLC.