Wang J.-B.,Harbin Medical University |
Liu F.-H.,Harbin Medical University |
Chen J.-H.,Harbin Medical University |
Ge H.-T.,Harbin Medical University |
And 4 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2017
Background: Long noncoding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to compete with mRNAs for binding miroRNAs (miRNAs). The dysregulated triplets, composed by mRNAs, lncRNAs, and miRNAs, contributed to the development and progression of diseases, such as cancer. However, the roles played by triplet biomarkers are not fully understand in glioblastoma multiforme (GBM) patient survival. Objectives: Here, we constructed a differential triplet interaction network (TriNet) between GBM and normal tissues and identified GBM survival related triplets. Methods: Four significantly dysregulated modules, enriched differentially expressed molecules, were identified by integrating affinity propagation method and hypergeometric method. Furthermore, knockdown of TP73-AS1 was implemented by siRNA and the expression of RFX1 was examined in U87 cells by qRT-PCR. The apoptosis of U87 cells was investigated using MTT assay and Acridine orange/Ethidium bromide (AO/EB) assay. Results: We randomly split GBM samples into training and testing sets, and found that these four modules can robustly and significantly distinguish low- and high-survival patients in both two sets. By manually curated literatures for triplets mediated by core interactions, we found that members involved tumor invasion, proliferation, and migration. The dysregulated triplets may cause the poor survival of GBM patients. We finally experimentally verified that knockdown of TP73-AS1, an lncRNA of one triplet, could not only reduce the expression of RFX1, an mRNA of this triplet, but also induce apoptosis in U87 cells. Conclusions: These results can provide further insights to understand the functions of triplet biomarkers that associated with GBM prognosis. © 2017 Springer-Verlag Berlin Heidelberg
PubMed | Harbin Medical University, Heilongjiang Academy of Medical science and Peking Union Medical College
Type: Journal Article | Journal: Oncotarget | Year: 2016
Colorectal cancer (CRC) is one of the most common solid tumors worldwide, often associated with inflammation. The microbes in the human intestine have a key role in inflammations and CRC. Chitotriose renders growth advantage to some bacteria, especially some pathogens, and thus has a role in inflammations. The enzyme chitotriosidase, encoded by the CHIT1 gene of the host, may degrade chitotriose with different efficiencies depending on the alleles. We sequenced the CHIT1 gene for 320 Chinese Han CRC patients and 404 normal controls, and focused on variations rs61745299 and rs35920428 within the CHIT1 gene for their possible roles in CRC. Statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). Multiple sequence alignment was conducted using the Vector NTI, and protein expression levels were analyzed by western blotting. The two variations, rs61745299 and rs35920428 within the CDS region of CHIT1 gene, were associated with the risk of CRC (both with P values < 0.001). Western blotting analysis showed that the variations increased the expression levels of the CHIT1 and C-reaction protein genes in the cancer tissue. We conclude that the two variations of CHIT1, rs61745299 and rs35920428, increase expression of the gene and are associated with CRC in Chinese Han populations.
Shi M.,Harbin Medical University |
Shi M.,Heilongjiang Academy of Medical science |
Yu B.,Harbin Medical University |
Gao H.,Daqing Oil Field General Hospital |
And 4 more authors.
Molecular Biology Reports | Year: 2013
Many studies investigated the relationship between matrix metalloproteinase 2 (MMP-2) overexpression and survival in patients with colorectal cancer (CRC), but yielded inconsistent results. To derive a more precise estimate of the prognostic significance of MMP-2 overexpression, we reviewed published studies and carried out a meta-analysis. Eligible articles were identified for the period up to March 2012 in electronic databases. To evaluate the correlation between MMP-2 overexpression and the prognosis in CRC, pooled hazard ratio (HR) and its 95% confidence interval (95% CI) for poorer overall and progression-free survival were appropriately derived from fixed-effects or random-effects models using standard meta-analysis techniques. Thirteen studies with a total of 1,919 CRC patients stratifying overall survival (OS) and/or progression-free survival in CRC patients by MMP-2 expression status were eligible for analysis. Ten studies investigated the OS in a total of 1,612 cases with CRC, and five studies investigated the progression-free survival in a total of 508 patients CRC. The combined HR estimate for OS and progression-free survival was 1.74 (95% CI, 1.34-2.26) and 1.35 (95% CI, 1.07-1.80), respectively. Both subgroup analyses and sensitivity analysis further identified the prognostic role of MMP-2 overexpression in patients with CRC. There was no evidence for publication bias. In conclusion, MMP-2 overexpression is associated with poorer overall and progression-free survival in patients with CRC. © 2012 Springer Science+Business Media Dordrecht.
Jiang Z.,Heilongjiang Academy of Medical science |
Jiang Z.,Harbin Medical University |
Muhammad S.,Harbin Medical University |
Wang X.,Heilongjiang Academy of Medical science |
Wang X.,Harbin Medical University
Chinese Journal of Cancer Research | Year: 2013
It is well known that one-stage resection of synchronous multiple primary colorectal carcinoma is an ideal choice if the patient's physical condition is not bad. Detailed examination of the whole intestinal tract is very important for patients with colorectal cancer, which could prevent patients from receiving repeat treatment to a great extent. We present a case report of a patient with synchronous primary colorectal cancer. Because pre- or intra-operative examination is not sufficient at his first consultation, the patient had undergone multiple operations after receiving chemotherapy, radiotherapy and intestinal stent insertion, which results in peritoneal adhesions formation. The preoperative placement of prophylactic ureteral catheters facilitated recognition of ureters in operation that assure the prevention of ureteral injuries. If not aware of the importance of detailed preoperative examination and standardized treatment can lead to wrong treatment as in this case. Prophylactic ureteral catheters might assist in their immediate recognition. © Chinese Journal of Cancer Research. All rights reserved.
Li C.,Harbin Medical University |
Cai S.,Fudan University |
Wang X.,Harbin Medical University |
Wang X.,Heilongjiang Academy of Medical science |
And 2 more authors.
PLoS ONE | Year: 2014
Background and Objectives: Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors. This study aims to investigate the role of TCF3 in predicting prognosis of patients with stage II and III colorectal cancer (CRC). Copyright:Methods: Real-Time quantitative PCR was performed in 64 fresh CRC tissues and 6 cell lines to examine TCF3 mRNA expression. TCF3 protein expression dynamics were detected by immunohistochemistry of 118 paraffin-embedded specimens, and the clinical significance of TCF3 was assessed by clinical correlation and Kaplan-Meier analyses. Aberrant hypomethylation of TCF3 promoter was also investigated using bisulfite sequencing and methylation specific PCR.Results: The up-regulation of TCF3 mRNA was frequently detected both in CRC tissues with recurrence and metastasisderived cell lines. The expression level of TCF3 protein was significantly correlated with histological type (P = 0.038) and disease-free survival time (P = 0.002). Higher TCF3 expression indicated poor prognostic outcomes (P<0.05, log-rank test). Multivariate analysis also showed strong TCF3 protein expression and perineural invasion were independent adverse prognosticators in CRC (P= 0.010, 0.000). Moreover, it was showed that promoter hypomethylation of TCF3 is associated with its up-expression.Conclusions: This study highlighted the prognostic value of TCF3 in stage II and III CRC. The up-regulation of TCF3, which is mainly caused by promoter hypomethylation, is one of the molecular mechanisms involved in the development and progression of CRC. © 2014 Li et al.
Chen M.,Harbin Medical University |
Liu Y.,Harbin Medical University |
Yi D.,Harbin Medical University |
Wei L.,Harbin Medical University |
And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2014
Background: Tanshinone IIA inhibits the proliferation of pulmonary artery smooth muscle cells (PASMCs), but the potential mechanisms of its effects on PASMCs apoptosis remain unclear. Methods: Rat were subjected to hypoxia for 9 days with or without Tanshinone IIA treatment. PASMCs were exposed to the conditions of 2% O2 and 93% N2 for 24 h in vitro. Hematoxylin and eosin (HE) staining was used to evaluate vascular remodeling. The Cell viability was determined using cell fluorescence staining and MTT assays, and apoptosis was assessed using flow cytometry. Protein expression was quantified by Western blotting. Results: Our results showed that Tanshinone IIA treatment reduced pulmonary artery media thickening in hypoxic rats. Tanshinone IIA reduced PASMC viability in a dose-dependent manner. Additionally, Tanshinone IIA promoted PASMC apoptosis, lowered Hsp60 levels, and upregulated caspase-3 expressions under hypoxic conditions. This pro-apoptotic effect of Tanshinone IIA might be due to the reduction of the phosphorylation of JAK2/STAT3 signaling markers and the increase in the levels of the downstream target, Cx43 in PASMCs. Conclusion: These data suggest that Tanshinone IIA promotes PASMC apoptosis during hypoxia and reverses vascular remodeling. This effect is mediated by modulating the expression of Hsp60, caspase-3, and Cx43 via the JAK2/STAT3 signaling pathway. These results might provide a new therapeutic target to explore a novel strategy for hypoxia-induced vessel remodeling. © 2014 S. Karger AG, Basel.
Liu Z.,Harbin Medical University |
Yan C.,Harbin Medical University |
Kang C.,Harbin Medical University |
Zhang B.,Harbin Medical University |
And 3 more authors.
PLoS ONE | Year: 2015
Purpose To evaluate the effect of trabecular thickness and trabecular separation on modulating the trabecular architecture of the mandibular bone in ovariectomized rats. Materials and Methods Fourteen 12-week-old adult female Wistar rats were divided into an ovariectomy group (OVX) and a sham-ovariectomy group (sham). Five months after the surgery, the mandibles from 14 rats (seven OVX and seven sham) were analyzed by micro-CT. Images of interradicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed. Results Compared to the sham group, trabecular thickness in OVX alveolar bone decreased by 27% (P = 0.012), but trabecular separation in OVX alveolar bone increased by 59% (P = 0.005). A thickness and separation map showed that trabeculae of less than 100μm increased by 46%, whereas trabeculae of more than 200μm decreased by more than 40% in the OVX group compared to those in the sham group. Furthermore, the OVX separation of those trabecular of more than 200μm was 65% higher compared to the sham group. Bone mineral density (P = 0.028) and bone volume fraction (p = 0.001) were also significantly decreased in the OVX group compared to the sham group. Conclusions Ovariectomy-induced bone loss in mandibular bone may be related to the distributional variations in trabecular thickness and separation which profoundly impact the modulation of the trabecular architecture. © 2015 Liu et al.
Shan M.,Harbin Medical University |
Shan M.,Heilongjiang Academy of Medical science |
Yin H.,Harbin Medical University |
Li J.,Harbin Medical University |
And 10 more authors.
Oncotarget | Year: 2016
Detection of breast cancer at an early stage is the key for successful treatment and improvement of outcome. However the limitations of mammography are well recognized, especially for those women with premenopausal breast cancer. Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we examined the promoter methylation of six genes (SFN, P16, hMLH1, HOXD13, PCDHGB7 and RASSF1a) in circulating free DNA (cfDNA) extracted from serum. We used a high-throughput DNA methylation assay (MethyLight) to examine serum from 749 cases including breast cancer patients, patients with benign breast diseases and healthy women. The sixgene methylation panel test achieved 79.6% and 82.4% sensitivity with a specificity of 72.4% and 78.1% in diagnosis of breast cancer when compared with healthy and benign disease controls, respectively. Moreover, the methylation panel positive group showed significant differences in the following independent variables: (a) involvement of family history of tumors; (b) a low proliferative index, ki-67; (c) high ratios in luminal subtypes. Additionally the panel also complemented some breast cancer cases which were neglected by mammography or ultrasound. These data suggest that epigenetic markers in serum have potential for diagnosis of breast cancer.
Liang X.,Harbin Medical University |
Sun S.,Harbin Medical University |
Zhang X.,Harbin Medical University |
Wu H.,Harbin Medical University |
And 6 more authors.
Cancer Science | Year: 2015
The aim of this study is to investigate the expression of ribosome-binding protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied using real-time quantitative PCR and western blotting using pair-matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P = 0.02), molecular subtype (P = 0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade-stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected overall survival in patients with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive patients with negative RRBP1 expression had longer overall survival rates than those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a valuable prognostic factor in Her-2-positive breast cancer patients, indicating that RRBP1 is a potentially important target for the prediction of prognosis. RRBP1 is a valuable prognostic factor in Her-2 positive breast cancer patients, indicating RRBP1 may be a potentially important target for the prediction of prognosis. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
PubMed | Harbin Medical University and Heilongjiang Academy of Medical Science
Type: | Journal: Journal of cellular and molecular medicine | Year: 2017
The clinical application of doxorubicin (Dox) is limited by its adverse effect of cardiotoxicity. Previous studies have suggested the cardioprotective effect of brain-derived neurotrophic factor (BDNF). We hypothesize that BDNF could protect against Dox-induced cardiotoxicity. Sprague Dawley rats were injected with Dox (2.5 mg/kg, 3 times/week, i.p.), in the presence or absence of recombinant BDNF (0.4 g/kg, i.v.) for 2 weeks. H9c2 cells were treated with Dox (1 M) and/or BDNF (400 ng/ml) for 24 hrs. Functional roles of BDNF against Dox-induced cardiac injury were examined both in vivo and in vitro. Protein level of BDNF was reduced in Dox-treated rat ventricles, whereas BDNF and its receptor tropomyosin-related kinase B (TrkB) were markedly up-regulated after BDNF administration. Brain-derived neurotrophic factor significantly inhibited Dox-induced cardiomyocyte apoptosis, oxidative stress and cardiac dysfunction in rats. Meanwhile, BDNF increased cell viability, inhibited apoptosis and DNA damage of Dox-treated H9c2 cells. Investigations of the underlying mechanisms revealed that BDNF activated Akt and preserved phosphorylation of mammalian target of rapamycin and Bad without affecting p38 mitogen-activated protein kinase and extracellular regulated protein kinase pathways. Furthermore, the beneficial effect of BDNF was abolished by BDNF scavenger TrkB-Fc or Akt inhibitor. In conclusion, our findings reveal a potent protective role of BDNF against Dox-induced cardiotoxicity by activating Akt signalling, which may facilitate the safe use of Dox in cancer treatment.