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1.
Katia R. M. Leite Denis R. Morais Sabrina T. Reis Nayara Viana Caio Moura Manuel Garcia Florez Iran A. Silva Nelson Dip Miguel Srougi 《Clinics (S?o Paulo, Brazil)》2013,68(6):797-802
OBJECTIVE:
MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines.METHODS:
Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A.RESULTS:
There was reduction in mTOR (p = 0.025), THAP2 (p = 0.038), SMARCA5 (p = 0.001) and BAZ2A (p = 0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p = 0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%.CONCLUSIONS:
We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future. 相似文献2.
Binghai Chen Lujing Duan Guangming Yin Jing Tan Xianzhen Jiang 《Clinics (S?o Paulo, Brazil)》2013,68(6):825-833
OBJECTIVES:
MiRNAs are intrinsic RNAs that interfere with protein translation. Few studies on the synergistic effects of miRNAs have been reported. Both miR-424 and miR-381 have been individually reported to be involved in carcinogenesis. They share a common putative target, WEE1, which is described as an inhibitor of G2/M progression. Here, we studied the synergistic effects of miR-424 and miR-381 on renal cancer cells.METHODS:
The viability of 786-O cells was analyzed after transfection with either a combination of miR-424 and miR-381 or each miRNA alone. We investigated cell cycle progression and apoptosis with flow cytometry. To confirm apoptosis and the abrogation of G2/M arrest, we determined the level of pHH3, which is an indicator of mitosis, and caspase-3/7 activity. The expression levels of WEE1, Cdc25, γH2AX, and Cdc2 were manipulated to investigate the roles of these proteins in the miRNA-induced anti-tumor effects. To verify that WEE1 was a direct target of both miR-424 and miR-381, we performed a dual luciferase reporter assay.RESULTS:
We showed that the combination of these miRNAs synergistically inhibited proliferation, abrogated G2/M arrest, and induced apoptosis. This combination led to Cdc2 activation through WEE1 inhibition. This regulation was more effective when cells were treated with both miRNAs than with either miRNA alone, indicating synergy between these miRNAs. WEE1 was verified to be a direct target of each miRNA according to the luciferase reporter assay.CONCLUSIONS:
These data clearly demonstrate that these two miRNAs might synergistically act as novel modulators of tumorigenesis by down-regulating WEE1 expression in renal cell cancer cells. 相似文献3.
Purpose
Apoptosis of vascular endothelial cells is a type of endothelial damage that is associated with the pathogenesis of cardiovascular diseases such as atherosclerosis. Heterotrimeric GTP-binding proteins (G proteins), including the alpha 12 subunit of G protein (Gα12), have been found to modulate cellular proliferation, differentiation, and apoptosis of numerous cell types. However, the role of Gα12 in the regulation of apoptosis of vascular cells has not been elucidated. We investigated the role of Gα12 in serum withdrawal-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its underlying mechanisms.Materials and Methods
HUVECs were transfected with Gα12 small-interfering RNA (siRNA) to knockdown the endogenous Gα12 expression and were serum-deprived for 6 h to induce apoptosis. The apoptosis of HUVECs were assessed by Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of microRNAs were analyzed by quantitative real-time PCR.Results
Knockdown of Gα12 with siRNA augmented the serum withdrawal-induced apoptosis of HUVECs and markedly repressed the expression of microRNA-155 (miR-155). Serum withdrawal-induced apoptosis of HUVECs was inhibited by the overexpression of miR-155 and increased significantly due to the inhibition of miR-155. Notably, the elevation of miR-155 expression prevented increased apoptosis of Gα12-deficient HUVECs.Conclusion
From these results, we conclude that Gα12 protects HUVECs from serum withdrawal-induced apoptosis by retaining miR-155 expression. This suggests that Gα12 might play a protective role in vascular endothelial cells by regulating the expression of microRNAs. 相似文献4.
Joji Watanabe Hiroaki Saito Kozo Miyatani Masahide Ikeguchi Yoshihisa Umekita 《Yonago acta medica》2015,58(3):137-143
Background
Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear.Methods
Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay.Results
Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator.Conclusion
TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. 相似文献5.
6.
Wang Y Liu Y Shen X Zhang X Chen X Yang C Gao H 《International journal of clinical and experimental pathology》2012,5(4):315-325
Purpose
To investigate the expression of the human PIWI subfamily proteins in gastric cancer and their potential roles in the occurrence, development and prognosis of gastric cancer.Methods and patients
Expression of the PIWI proteins were assessed by immunohistochemistry (IHC) in tissue microarrays (TMA), containing paired tumor tissue and adjacent non-cancer tissue from 182 patients who had undergone surgery in hospital for histologically proven gastric cancer (GC). Prognostic value and correlation with other clinicopathologic factors were evaluated in two classifications.Results
The expression of PIWIL1-4 was significantly higher in tumor tissue than that in adjacent tissue; A significant correlation was observed between the higher expression of PIWI protein with the T stage, lymph node metastasis and clinical TNM (cTNM); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated PIWIL1 and PIWIL2 expression in cancer tissue predicted poorer overall survival (OS) compared with group in lower expression (36.5% VS 67.6%; 37.4% VS 54.2%; respectively). Notably, multivariate analyses by Cox’s proportional hazard model revealed that expression of PIWIL1 was an independent prognostic factor in gastric cancer.Conclusions
The PIWI subfamily protein is an absolutely key molecular factor along with the tumor occurrence and development. And the PIWI protein could act as a potential biomarker for prognosis evaluation of gastric cancer. 相似文献7.
Yusuke Kanda Tokuichi Kawaguchi Mitsuhiko Osaki Kunishige Onuma Takahiro Ochiya Tomoyuki Kitagawa Futoshi Okada 《Inflammation research》2018,67(10):839-846
Objective
In sporadic colon tumors, multistep process of well-known genetic alterations accelerates carcinogenesis; however, this does not appear to be the case in inflammation-related ones. We previously established a model of inflammation-related colon carcinogenesis using human colonic adenoma cells, and identified fascin as a driver gene of this process. We analyzed the microRNAs involved in the stable fascin expression in colon adenocarcinoma cells.Materials and methods
miRNA microarray analysis was performed using FPCK-1-1 adenoma cells and its-derived FPCKpP1-4 adenocarcinoma cells through chronic inflammation. To assess the involvement of miRNA in the inflammation-related carcinogenesis, sphere-forming ability, expression of colon cancer stemness markers, and stability of fascin protein via the proteasome using tough decoy RNA technique.Results
We found that 17 miRNAs including miR-146a were upregulated and 16 miRNAs were downregulated in FPCKpP1-4 adenocarcinoma cells. We revealed that miR-146a in the adenocarcinoma cells brought about acquisition of sphere formation, cancer stemness, and inhibition of proteasomal degradation of the fascin protein.Conclusions
We found that stable fascin expression is brought about via the inhibition of proteasome degradation by miR-146a in the process of a chronic inflammation-related colon carcinogenesis.8.
Tomasz Powrózek Radosław Mlak Marcin Dziedzic Teresa Małecka-Massalska Dariusz Sagan 《Pathology, research and practice》2018,214(3):368-373
Introduction
MicroRNA (miRNA) are attractive markers of lung cancer, due to their regulatory role in cell cycle. However, we know more about function of miRNA in cancer development, there is still little known about role of their precursors (primary miRNA; pri-miRNA) in tumorgenesis. In present study we investigated potential role of miRNA-944 and its precursor pri-miRNA-944 in development of squamous-cell lung cancer (SCC) and explored interdependence between miRNA precursor and its mature form. This is a first available literature report analyzing pri-miRNA as a cancer diagnostic marker.Material and methods
Expression of miRNA-944 and its precursor was analyzed in 58 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using qRT-PCR. Expression of pri-miRNA-944 was correlated with TP63 and miRNA-944. Using ROC analysis diagnostic accuracy of studied markers was evaluated.Results
miRNA-944 and its precursor were significantly overexspressed in SCC compared to adenocarcinoma (AC) and non-cancerous tissue. pri-miRNA-944 strongly and positively correlated with TP63 (r?=?0.739, p?<?0.001) and with mature miRNA-944 expression (r?=?0.691, p?<?0.001). Also, TP63 expression significantly correlated with mature miRNA (r?=?0.785, p?<?0.001). Combined analysis of pri-miRNA-944 and mature miRNA-944 allowed to distinguish SCC tissue form AC with sensitivity of 93.3% and specificity of 100% (AUC?=?0.978), and SCC from non-cancerous tissue with 92.9% sensitivity and 100% specificity (AUC?=?0.992).Conclusion
We assumed that pri-miRNA-944 and miRNA-944 may be involved in early squamous-type differentiation of lung tumors. Moreover, analysis of both markers provided high diagnostic accuracy for SCC detection. 相似文献9.
Introduction
Gastric cancer is the second leading cause of cancer death in the world. The objective of this study was to present the clinical evaluation, treatment and outcome of 179 patients with gastric carcinoma in Zaria, Nigeria.Methods
Patients managed for histologically diagnosed gastric carcinoma were reviewed. The extent of surgical intervention was based on pre-operative and intra-operative staging balanced against the age and overall fitness of the patient. Mortality, morbidity and patient''s survival were monitored.Results
There were 179 patients, with a male to female ratio of 1.4:1. Their mean age was 51±6.3. Ten (5.6%) patients presented with early gastric cancer. Overall, 155(86.6%) patients had surgical intervention including gastric resection in 87 (56.1%). Of the gastrectomies , 28.7% were curative (R0). Postoperative complications were seen in 43(27.7%) patients. Postoperative mortality in 25(16.1%) patients was significantly associated with peritoneal metastasis (p<0.001), preoperative comorbidity (p<0.01) and age more than 60years (p<0.03). The overall median survival was 13.6 months while 70.1% and 21.8% of patients that underwent gastrectomy survived for 1 and 5 years respectively.Conclusion
Treatment of gastric cancer should be based on a reasonable choice of operation that must consider not only the survival benefits but also the surgical risks and postoperative quality of life 相似文献10.
BS Hu HF Yu G Zhao TZ Zha 《International journal of clinical and experimental pathology》2012,5(7):668-673
Aim
To investigate the expression and prognostic significance of RSF-1 in gastric adenocarcinoma.Methods
RSF-1 expression was analyzed using immunohistochemical staining on tissue samples from a consecutive series of 287 gastric adenocarcinoma patients who underwent tumor resections between 2003 and 2006.The relationship between RSF-1 expression, clinicopathological factors, and patient survival was investigated.Results
Immunohistochemical staining indicated that RSF-1 is highly expressed in 52.6% of gastric adenocarcinomas. RSF-1 expression levels were closely associated with tumor size, histological differentiation, tumor stage, and lymph node involvement. Kaplan-Meier survival analysis showed that high RSF-1 expression exhibited a significant correlation with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis revealed that RSF-1 expression is an independent prognostic parameter for the overall survival rate of gastric adenocarcinoma patients.Conclusion
Our data suggest that RSF-1 plays an important role in gastric adenocarcinoma progression and that high RSF-1 expression predicts an unfavorable prognosis in gastric adenocarcinoma patients. 相似文献11.
Hua Huang Juan Wu Guangfu Jin Hanze Zhang Yanbing Ding Zhaolai Hua Yan Zhou Yan Xue Yan Lu Zhibin Hu Yaochu Xu Hongbing Shen 《生物医学研究杂志》2010,24(2):100-106
Objective
Inflammation induced by H.pylori colonization in the stomach is related to the development of gastric cancer and the genetic variations of the genes involved in the immune responses modify the host response to the infection. The aim of this study was to evaluate whether polymorphisms in the toll-like receptor 4 (TLR4) gene, a key regulator of both innate and adaptive immunity, were related to the susceptibility to gastric cancer in a Chinese population.Methods
Two variations in the 5′-flanking region of TLR4 (rs1927914 T > C and rs10759932 T > C) were genotyped by using the PCR-restriction fragment length polymorphism (RFLP) assay in a case-control study of 1,053 incident gastric cancer cases and 1,100 cancer-free controls in a Chinese population.Results
Individuals carrying the C allele of rs10759932 had a significantly reduced risk of gastric cancer (adjusted OR = 0.81; 95%CI = 0.67-0.96), compared with the wild-type homozygote (TT), and the protective effect was not significantly different among subgroups stratified by age, sex, smoking, drinking and H.pylori infection status (P for heterogeneity > 0.05). No significant association was observed between rs1927914 and gastric cancer risk in this study population.Conclusion
The T to C allele substitution of rs10759932 may play a protective role in gastric carcinogenesis in a Chinese population. Large studies with different ethnic populations are warranted to confirm these findings. 相似文献12.
13.
Background
Breast cancer is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying breast cancer metastasis are still incompletely clear. MicroRNAs (miRNAs) play a crucial role in cancer metastasis. In this study, we aimed to analyze the expression and function of miR-449a in breast cancer.Material and methods
A total of 15 human primary breast cancer tissues and adjacent non-cancerous tissues (10 pairs) were obtained. MiR-449a was examined in tumor tissues and adjacent nontumorous tissues of breast cancer patients and cell lines by real-time PCR. The protein expression levels were analyzed by western blot and immunohistochemistry staining. Luciferase reporter assays was used to validate the target of miR-449a. The effect of miR-449a on breast cancer cell migration and invasion were studied in vitro and in vivo.Results
The expression levels of miR-449a were significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-449a suppressed breast cancer cell proliferation, clone formation, migration, invasion and metastasis in vitro and in vivo. Pleomorphic adenoma gene like-2 (PLAGL2) was identified as a major target of miR-449a. Both overexpression of miR-449a inhibited the expression of PLAGL2 significantly and the knockdown of PLAGL2 expression inhibited the breast cancer cell proliferation and metastasis.Conclusion
We demonstrate the miR-449a tumor suppressor role in breast cancer cell migration and invasion via targeting PLAGL2. These findings suggesting that miR-449a/PLAGL2 could serve as a therapeutic strategy for targeting breast cancer. 相似文献14.
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17.
Yue Zhu Ying Han Tian Tian Peihong Su Guan Jin Juan Chen Yungui Cao 《Pathology, research and practice》2018,214(3):374-379
Objective
This study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications.Methods
Specimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA. The expression levels of the miR-21-5p and miR-34a were detected by RT-PCR. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH). Then miRNA, hTERC expressions were compared with the cytological and histologic examination.Results
Compared to that in the benign samples, the expression of miR-21-5p and miR-34a in abnormal samples was significantly upregulated and downregulated, gradually corresponding to the severity of cervical lesions (P?<?0.05). There was a trend toward an increasing amplification of hTERC with the increasing severity of cervical lesions. miR-21-5p and miR-34a expression, and hTERC amplification were more specific than HPV positivity in differentiating low-grade cervical disorders from high-grade ones (P?<?0.05).Conclusions
MiR-21-5p upregulation, miR-34a downregulation, and hTERC amplification were associated with the aggressive progression of CC, which suggests that miR-21-5p, miR-34a and hTERC might serve as surrogate markers for CC progression and potential molecular targets for blockage of the development of CC. 相似文献18.
Zhi Ding Haitao Lan Rui Xu Xiang Zhou Yong Pan 《Pathology, research and practice》2018,214(12):1993-1999
Background
Long noncoding RNAs (lncRNAs) have been considered as significant regulators in many cancer progression, such as proliferation, invasion and other path of evolution. Nevertheless, we have not had a grasp of the role of lncRNA TP73-AS1 in gastric cancer (GC).Methods
qRT-PCR analysis was first conducted to examine the TP73-AS1 level in both GC tissues and cell lines. Then gain or loss-of-function assays were carried out to detect the effect of TP73-AS1 on GC development. In mechanism, bioinformatics analysis and luciferase reporter assays were used to search and confirm the target gene of TP73-AS1. Finally, rescue assays were performed to confirm the influence of TP73-AS1-miR-194-5p-SDAD1 axis on GC development.Results
TP73-AS1 was upregulated in GC tissues and cell lines. Furthermore, TP73-AS1 exerted oncogenic role in GC through promoting cell growth and metastasis. In addition, TP73-AS1 was certified as a ceRNA by regulating miR-194-5p/SDAD1 axis.Conclusions
TP73-AS1 accelerates tumor progression in gastric cancer through regulating miR-194-5p/SDAD1 axis. 相似文献19.
Xiangwen Zhang Tingting Zhou Wenbin Li Taotao Zhang Ninwei Che Guo Zu 《Pathology, research and practice》2018,214(8):1105-1109
Background
Few studies have reported the clinical and prognostic significance of C/EBP homologous protein (CHOP) in advanced gastric cancer (GC). Therefore, the present study investigated the expression of CHOP in advanced GC patients to determine its potential prognostic role.Methods
The levels of CHOP in 95 patients with advanced GC and adjacent non-cancerous tissues were evaluated by qRT-PCR, western blot and immunohistochemistry. Furthermore, the association of CHOP expression with clinicopathological parameters and prognosis of advanced GC patients was analyzed.Results
The levels of CHOP were down-regulated in advanced GC compared with non-cancerous tissues (P<0.01). In addition, high CHOP expression more frequently occurred in advanced GC tissues with depth of invasion of T1-2 (P?<?0.01), lower clinical stage (TNM Ⅰ-Ⅱ stage) (P<0.05) and without lymph node metastasis (P<0.05). No significant difference was observed between the expression of CHOP and age, gender, tumor size, lesion site and differentiation (P>0.05). The Kaplan-Meier survival analyses showed that the overall survival rate of advanced GC patients with positive CHOP expression was significantly higher than that of patients with negative CHOP expression (P<0.01). Univariate and multivariate Cox proportional hazards models revealed that low CHOP expression (OR?=?0.314, 95%CI: 0.176～0.794, P?=?0.003) was an independent factor for poor overall survival in advanced GC patients.Conclusion
Low expression of CHOP predicts the poor prognosis of advanced GC patients, and CHOP may be a prognostic biomarker for patients with advanced GC. 相似文献20.
Geping Wu Guanghai Yang Ruxin Zhang Guangyin Xu Ling Zhang Wu Wen Jianbing Lu Jianyong Liu Yan Yu 《Allergy, asthma & immunology research》2015,7(5):449-457