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Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion.
The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.
Authors: Yuan, Jianfen | Xiao, Chunhong | Lu, Huijun | Yu, Haizhong | Hong, Hong | Guo, Chunyan | Wu, Zhimei
Article Type: Research Article
Abstract: Breast cancer is one common female specific malignant tumor and has gradually increased incidence. Matrix metalloproteinase-9 (MMMP-9) and its inhibitor TIMP-1 participate in tumor invasion and metastasis. This study analyzed the effect of various treatment approaches on TIMP-1 and MMP-9 levels in terminal stage breast cancer. Post-op breast cancer patients including chemo-radio therapy group, radio-chemo therapy group and simultaneously chemo- and radio-therapy group were compared for efficacy, along with assays for TIMP-1 and MMP-9 levels for analyzing their correlation with clinical-pathological features of breast cancer. Chemo + radio-therapy group had lower focal recurrence and distal metastasis than …the other two groups, plus higher 5-year survival rates (p < 0.05). After treatment, all patients showed lower serum MMP-9 level, activity and higher TIMP-1 levels than those before treatment (p < 0.05). Concurrent radio + chemo-therapy group showed lower serum MMP-9 level, activity and higher TIMP-1 levels (p < 0.05 compared to the other two groups). Serum MMP-9 and TIMP-1 levels after treatment are correlated with patient age, pathological grade, tumor size and lymph node metastasis (p < 0.05). Simultaneous chemo- and radio-therapy on breast cancer patients after surgery could reduce focal recurrent rate or distal metastasis rate, thus improving 5-year survival rate. MMP-9 and TIMP-1 levels are correlated with age, pathological grade, tumor size and lymph node metastasis of breast cancer patients. Show more
Keywords: Breast cancer, treatment efficacy, TIMP-1, MMP-9
DOI: 10.3233/CBM-170901
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 1-7, 2018
Authors: Ni, Wei | Luo, Lin | Zuo, Ping | Li, Ren-Ping | Xu, Xiao-Bing | Wen, Fan | Hu, Dong
Article Type: Research Article
Abstract: This article has been retracted, and the online PDF replaced with this retraction notice.
Keywords: lncRNAs, numb, GHET1, biological activities, vitro study, vivo study
DOI: 10.3233/CBM-171002
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 9-22, 2018
Authors: Li, Xin | Ma, Wenyi | Wang, Xiaojie | Ci, Yunzhe | Zhao, Yina
Article Type: Research Article
Abstract: BACKGROUND: Annexin A5 (ANXA5) is a kind of Ca 2 + -dependent phospholipid binding protein which is involved in cell membrane dynamics and organization. Recent data showed that ANXA5 might involve in tumorigenesis. OBJECTIVE: To explore what role ANXA5 play in human uterine cervical carcinoma. MATERIALS AND METHODS: In this study, a recombined ANXA5 plasmid was constructed and uterine cervical carcinoma cell lines HeLa and SiHa were transfected with it. After ANXA5 overexpression was determined by Western Blot, cell proliferation test was detected by MTT assay and colony formation …assay respectively. FACS assay and Hochest33258 staining methods were employed to detect cell apoptosis. To further investigate whether ANXA5 influence cell migration and invasion, wound healing assay and transwell assay were applied. At the same time, the relative mechanism was investigated. RESULTS: When ANXA5 expression increased, cell proliferation was inhibited by regulating the expression of bcl-2 and bax while cell metastasis was suppressed by regulating E-cadherin and MMP-9 expression. CONCLUSION: ANXA5 overexpression in the uterine cervical carcinoma might play important roles in cell proliferation and metastasis of uterine cervical cancer cells and act as an anti-cancer gene in uterine cervical cancer. Show more
Keywords: ANXA5, uterine cervical carcinoma cell, proliferation, apoptosis, invasion, migration
DOI: 10.3233/CBM-171040
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 23-32, 2018
Authors: Zhang, Meng-Hui | Niu, Hu | Li, Zheng | Huo, Ren-Tao | Wang, Jun-Mei | Liu, Jun
Article Type: Research Article
Abstract: OBJECTIVE: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy that has a poor prognosis. Through the literatures, TINAG significantly participated in the processes of the renal-associated diseases, but there were no studies about the roles of TINAG in the HCC development. Hence, we attempted to use the HCC samples collected by ourselves to reveal the clinical significance and prognostic impact of TINAG in HCC. METHODS: We first measured the expression level of TINAG in HCC on the basis of TCGA database. Then, real time quantitative reverse transcription PCR (RT-qPCR) was used to examine the expression level …of TINAG in 100 pairs of HCC tissues and corresponding adjacent non-tumor tissues, as well as HCC cell lines (HepG2, HB611, HHCC, and Hep3B). Moreover, Kaplan-Meier method and COX’s proportional hazards model were utilized to perform the survival and prognosis analyses using the clinical data collected by ourselves. After knockdown of TINAG, the cell proliferation, invasion and migration capacities of HepG2 and Hep3B cells were evaluate by counting kit-8 (CCK-8) assay (24 h, 48 h, 72 h, and 96 h post-cultivation), clone formation experiment, would-healing, and invasion as well as migration assays. To further explore whether the dys-regulated TINAG expression regulates the HCC progression and prognosis, protein biomarkers of PI3K signaling pathway, including AKT, p-AKT, PI3K, p-PI3K, p70S6K, and p-p70S6K were measured based on western blotting analysis. RESULTS: According to the data of TCGA database, clinical patients, and HCC cell lines, TINAG was highly expressed in HCC compared with normal. Relationship of TINAG expression level with the clinicopathological factors implicated that the high expression of TINAG was significantly associated with pathologic stage, pathologic-node, and pathologic-metastasis. Univariate as well as multivariate COX analysis indicated that TINAG expression and pathologic metastasis can serve as the independent prognostic factor for overall survival of HCC. After TINAG knockdown in HepG2 and Hep3B cells, cell proliferation rate, the colony numbers, and the invasive and migratory capacity were found to be suppressed. Remarkably, western blot results showed that reduction of TINAG remarkably decreased p-AKT, p-PI3K, and p-p70S6K expression level in HepG2 and Hep3B cells. CONCLUSION: Collectively, our results underscore the significance of TINAG in HCC progression and prognosis, and TINAG might be a novel candidate oncogene in HCC. These results propose that targeting TINAG might offer future clinical utility in HCC. Show more
Keywords: TINAG, hepatocellular carcinoma, proliferation, invasion, migration
DOI: 10.3233/CBM-181277
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 33-43, 2018
Authors: Li, Jian | Ma, Rui | Cao, Zhenbin | Zhang, Dongmei
Article Type: Research Article
Abstract: OBJECTIVE: To investigate the correlations of magnetic resonance imaging (MRI) manifestations with survivin gene expression in primary hepatocellular carcinoma (HCC). METHODS: A total of 84 HCC patients receiving partial hepatectomy in the Surgery Department and Oncology Department in our hospital from April 2011 to May 2014 were recruited. At 1 week before operation, MRI was used to examine the imaging features of liver, a certain size of area was defined and the signal value of each sequence was recorded. HCC and para-carcinoma tissues were collected after operation, and the expression levels of survivin were detected via immunohistochemistry (IHC). …All patients were followed up for 30 months after operation, and the Kaplan-Meier survival curve was drawn. The correlations of survivin expression with MRI features and signal parameters of each sequence were analyzed. RESULTS: There was no expression of survivin in normal liver tissues. In HCC and para-carcinoma tissues, the nuclei of positive cells showed brown yellow. The positive expression rate of survivin in HCC tissues was 76.19% (64/84), which was significantly higher than that in para-carcinoma tissues (20.81%, 20/84) (p < 0.05). The overall survival (OS) of patients with high expression of survivin was 12.5 months, which was significantly shorter than that of patients with low expression of survivin (17.6 months) (p < 0.05). Results of chi-square test showed that the survivin level had no correlations with the MRI scan shape and edge in the tumor area (p > 0.05), but it was significantly correlated with tumor diameter, MRI enhancement features and lymphatic metastasis (p < 0.05). Pearson correlation analyses revealed that the survivin IHC score was not correlated with in-phase T1-weighted gradient-recalled echo (GRE), hepatic arterial-phase T1-weighted GRE, portal venous-phase T1-weighted GRE and equilibrium-phase T1-weighted GRE signals (p > 0.05). Besides, the survivin IHC score was negatively correlated with opposed-phase T1-weighted GRE (r = - 0.46, p = 0.038), but positively correlated with T2-weighted fast spin echo signal (r = - 0.49, p = 0.025). CONCLUSION: Survivin is significantly up-regulated in HCC tissues and associated with tumor growth and lymph node metastasis. Clinical detection of survivin level combined with MRI examination might be beneficial for clinical diagnosis and treatment of HCC. Show more
Keywords: Primary hepatic carcinoma, magnetic resonance imaging (MRI), survivin, prognosis
DOI: 10.3233/CBM-181285
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 45-51, 2018
Authors: Pang, Lan | Wang, Jing | Fan, Yong | Xu, Rui | Bai, Yuping | Bai, Liangcai
Article Type: Research Article
Abstract: OBJECTIVE: To investigate the correlations of expression of vascular endothelial growth factor (VEGF) in gastric cancer tissues of patients and magnetic resonance imaging (MRI) features with clinical tumor-node-metastasis (TNM) staging and lymph node metastasis, and to analyze the diagnostic value of MRI features for preoperative TNM staging and lymph node metastasis of patients with gastric cancer, and the roles of VEGF in tumor development and metastasis. METHODS: A total of 120 gastric cancer patients treated in our hospital from May 2015 to July 2017 were selected as objects of study. The VEGF protein expressions in gastric cancer …tissues of patients with different TNM staging and lymph node metastasis degrees were detected using immunohistochemical method, and the correlations of VEGF protein expression with TNM staging and lymph node metastasis were analyzed. Before operation, MRI was used to predict TNM staging and lymph node metastasis of all patients, and prediction results were compared with postoperative pathological diagnosis results. At the same time, the differences in lymph node apparent diffusion coefficient (ADC), long diameter and short diameter, relative ADC of primary lesion (rADCp) and relative ADC of muscle (rADCm) were compared and analyzed between lymph node metastasis group and non-lymph node metastasis group. RESULTS: The VEGF expression in patients with stage-N3 gastric cancer was about 7 times that in patients with stage-N0 gastric cancer, and it was increased with the increased degree of lymph node metastasis (p < 0.01). The VEGF expression in patients with distant metastasis of tumor cells was significantly higher than that in patients without distant metastasis (p < 0.01). The expression of VEGF in stage-T4 gastric cancer was about 10 times that in stage-Tis cancer, and the larger the infiltration depth of tumor cells was, the higher the expression level of VEGF would be (p < 0.01). The VEGF expression in gastric cancer tissues was positively correlated with the infiltration depth, lymph node metastasis and distant metastasis of tumor cells. Moreover, the prediction results of MRI for TNM staging and lymph node metastasis before operation were compared with postoperative pathological results, and it was found that there was better consistency (Kappa = 0.739). ADC, rADCp and rADCm in gastric cancer patients without lymph node metastasis were significantly higher than those in patients with lymph node metastasis, but the short diameter and long diameter were obviously shorter than those in patients with lymph node metastasis, and the differences were statistically significant (p < 0.05). CONCLUSION: The VEGF protein expression in gastric cancer tissues is positively correlated with TNM staging and lymph node metastasis in patients. The preoperative prediction results of MRI are well consistent with postoperative pathological results, and MRI features are correlated with lymph node metastasis in patients, which has an important guiding significance for the diagnosis and treatment of gastric cancer. Show more
Keywords: Gastric cancer, TNM staging, lymph node metastasis, VEGF, MRI
DOI: 10.3233/CBM-181287
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 53-59, 2018
Authors: Zare, Razieh | Malekzadeh, Mahyar | Hashemi, Mohamad | Khademi, Bijan | Andishe-Tadbir, Azadeh
Article Type: Research Article
Abstract: BACKGROUND: Interleukin-33 (IL-33) has been recently discovered as an influential factor in the process of tumor immunity, and is presented in cancer pathogenesis. OBJECTIVE: This study aimed to determine the serum levels of IL-33 in patients with benign and malignant Salivary gland tumors (SGTs). METHODS: This descriptive cross-sectional study was performed on 47 samples of malignant SGTs including 18 mucoepidermoid carcinoma (MEC), 8 adenoid cystic carcinoma (ADCC), 21 malignant mixed tumor (MMT), and 14 benign pleomorphic adenoma (PA). A control group was considered consisting of 28 healthy subjects. The serum level of IL-33 was measured by using sandwich ELISA …method. The data were statistically analyzed through Kruskal-Wallis and Mann-Whitney tests. RESULTS: The median concentration of IL-33 was 6.91 in malignant, 5.14 in benign, and 5.01 in healthy cases, with a statistically significant difference (P = 0.001). The median serum levels of IL-33 increased significantly in ADCC (7.15), MEC (7.03), and MMT (6.91) compared with the control group (5.01) (P < 0.05). The mean rank of MEC was significantly higher than PA (P = 0.01). IL-33 concentration was positively and significantly correlated with the tumor stage (P = 0.02) and tumor size (P = 0.03). CONCLUSIONS: IL-33 could be suggested as a novel biomarker to distinguish different types of SGTs. Show more
Keywords: Salivary gland tumor, IL-33, malignant, benign, biomarker
DOI: 10.3233/CBM-181309
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 61-65, 2018
Authors: Wang, Xiaohui | Qu, Huajun | Dong, Yinghe | Wang, Guozhi | Zhen, Yuchen | Zhang, Linxia
Article Type: Research Article
Abstract: Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. To define molecular mechanisms of vemurafenib resistance, we generated A375-R, WM35-R cell lines resistant to vemurafenib and show that the phosphorylated (p)-STAT3 was upregulated in these cells in vitro and in vivo . In particular, activation of the Signal-transducer-and-activator-of-transcription 3 (STAT3) pathway was associated with vemurafenib resistance. Inhibition of this pathway with STAT3-specific siRNA (shRNA) sensitized A375-R, WM35-R cells to vemurafenib and induced apoptosis in vitro and in vivo . Moreover, targeting STAT3 induced expression of miR-579-3p …and elicited resistance to vemurafenib. However, targeting microRNA (miR)-579-3p with anti-miR-579-3p reversed the resistance to vemurafenib. Together, these results indicated that STAT3-mediated downexpression of miR-579-3p caused resistance to vemurafenib. Our findings suggest novel approaches to overcome resistance to vemurafenib by combining vemurafenib with STAT3 sliencing or miR-579-3p overexpression. Show more
Keywords: Melanoma, BRAF V600E inhibitor, Signal-transducer-and-activator-of-transcription 3, miR-579-3p
DOI: 10.3233/CBM-181365
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 67-77, 2018
Authors: Dou, Daoqin | Yang, Shaohua | Lin, Yunzheng | Zhang, Jiren
Article Type: Research Article
Abstract: PURPOSE: The purpose of this study was to establish a risk scoring system based on miRNAs to evaluate the prognosis in pancreatic adenocarcinoma. METHODS: Using a miRNA microarray dataset (179 pancreatic adenocarcinoma specimens and 4 normal control specimens) from TCGA, differentially expressed miRNAs were identified. Cox proportional hazards regression analysis was used to identify significant prognostic miRNAs, with which a risk scoring system was established and tested on a validation set. Cox regression analysis was performed to identify independent predictors of survival from clinical characteristics. Stratified Cox regression analyses were conducted to unravel the associations of clinical characteristics …with survival. Differentially expressed genes (DEGs) were screened followed by functional annotation of the DEGs. RESULTS: Eight miRNAs (miR-1301, miR-598, miR-1180, miR-155, miR-496, miR-203, miR-193b, miR-135b) were independent predictors for survival. A risk scoring system was established with the 8 signature miRNAs. Upon Cox multivariate regression analysis, risk score, new tumor and targeted molecular therapy were independent predictors of prognosis. Stratified Cox regression analyses found that targeted molecular therapy and new tumor are associated with survival of patients. Survival-related DEGs were significantly enriched with regulation of transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway. CONCLUSIONS: The study proposes 8-miRNA expression-based risk scoring system to predict prognosis in pancreatic adenocarcinoma. New tumor and targeted molecular therapy were independent predictors of prognosis. Transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway may be related to prognosis in pancreatic adenocarcinoma. Show more
Keywords: miRNA, prognosis, pathway, risk score, stratified analyses
DOI: 10.3233/CBM-181420
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 79-93, 2018
Authors: Mou, Yonghua | Wang, Dongguo | Xing, Renwei | Nie, Hanqiu | Mou, Yiping | Zhang, Yang | Zhou, Xianfei
Article Type: Research Article
Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancer worldwide and chronic infection of hepatitis B virus (HBV) serve as one of leading causes of HCC. OBJECTIVE : This study aimed to identify the novel long noncoding RNAs (lncRNAs) biomarkers for HBV-associated HCC. METHODS: The lncRNA and mRNA expression profiles of HCC patients with HBV infection were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between HCC and adjacent tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for HCC were identified by …using feature selection procedure and classification model. Functional annotation of DEmRNAs co-expressed with these lncRNAs biomarkers were performed. Receiver operating characteristic (ROC) curve and survival analysis of these lncRNAs biomarkers were performed. qRT-PCR validation was performed. RESULTS: A total of 82 DElncRNAs and 805 DEmRNAs between HBV-associated HCC and normal tissues were identified. CAPN10-AS1, LINC01093, RP5-890E16.2, FENDRR and C17orf82 were selected as optimal diagnostic and prognostic lncRNA biomarkers for HBV-associated HCC that were co-expressed with 105, 86, 70, 30 and 1 DEmRNAs, respectively. Based on the DEmRNAs co-expressed with these five lncRNAs biomarkers, Jak-STAT signaling pathway and retinol metabolism were two significantly enriched pathways. The result in qRT-PCR validation were consistent with our analysis based on TCGA, generally. CONCLUSIONS: This study identified five potential lncRNAs biomarkers for HBV-associated HCC with great diagnostic and prognostic value and provided clues for their functions in HBV-associated HCC. Show more
Keywords: Hepatocellular carcinoma (HCC), hepatitis B virus (HBV), biomarker, long noncoding RNAs (lncRNAs)
DOI: 10.3233/CBM-181424
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 95-106, 2018
Authors: Cheng, Jin-Zhang | Chen, Jun-Jun | Wang, Zong-Gui | Yu, Dan
Article Type: Research Article
Abstract: This article has been retracted, and the online PDF replaced with this retraction notice. doi: 10.3233/CBM-220951
Keywords: microRNA-185, HOXC6, TGF-β1/mTOR axis, nasopharyngeal carcinoma, proliferation, apoptosis, autophagy
DOI: 10.3233/CBM-181459
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 107-123, 2018
Authors: Baranova, Ivana | Kovarikova, Helena | Laco, Jan | Dvorak, Ondrej | Sedlakova, Iva | Palicka, Vladimir | Chmelarova, Marcela
Article Type: Research Article
Abstract: BACKGROUND: Aberrant DNA methylation of protocadherins (PCDHs) has been associated with development and progression of various types of cancer. It could represent possible direction in the search for critically needed tumor biomarkers for ovarian cancer. OBJECTIVE: To investigate methylation of δ 2 group of non-clustered PCDHs in high-grade serous ovarian carcinoma (HGSOC) tissue in comparison with control tissue. METHODS: We used next-generation sequencing for detecting regions with the most altered methylation. For further confirmation of discovered alterations we used methylation-sensitive high-resolution melting analysis. RESULTS: PCDH17 methylation was detected …in almost 70% of HGSOC patients without any methylation in the group of control samples and was found both in the late stage tumors as well as in the early stage ones. Other selected PCDHs did not show any relevant changes in methylation. Subsequent gene expression analysis of PCDH17 revealed decreased expression in all of the tumor samples in comparison to the control ones. Statistically significant negative correlation was found between methylation and levels of expression suggesting potentially methylation-based silencing. CONCLUSIONS: Methylation of PCDH17 could play an important role in development and progression of HGSOC and has potential to become a target in the search for new clinical biomarkers. Show more
Keywords: Ovary, high-grade serous carcinoma, methylation, protocadherin, next-generation sequencing, biomarker
DOI: 10.3233/CBM-181493
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 125-133, 2018
Authors: Kim, Yi Rang | Byun, Mi Ran | Choi, Jin Woo
Article Type: Research Article
Abstract: BACKGROUND: Hepatitis B virus (HBV) accounts for more than 60% of hepatocellular carcinoma (HCC) cases. However, there is limited information about the features of HBV-driven HCC that differentiate it from other types of HCC. OBJECTIVE: The aim of this study is to find a gene specific to HBV-driven HCC and understand its role during tumorigenesis. METHODS: The differences in gene expression patterns were analyzed among patients with hepatitis virus-unrelated liver cirrhosis, and hepatitis C virus- and HBV-driven HCC. Genes expressed only in HBV patients were compared to genes of transgenic mice expressing hepatitis …B viral X gene. RESULTS: Integrin α 6 was commonly overexpressed in both HBV-driven HCC patients and transgenic mice expressing viral X. This gene’s activation induced overexpression of integrin α 6, as well as formation of integrins α 6β 1 and α 6β 4, without changing the expression of non-integrin laminin receptors. Suppression of integrin α 6 caused significant inhibition of tumor migration in vitro . CONCLUSIONS: This study found a significant association between HBV and integrin α 6, which may be responsible for early migration and invasion of HCC. Thus, integrin α 6 is a predictive marker for tumor recurrence and invasiveness of HBV-driven HCC. Show more
Keywords: Hepatocellular carcinoma, integrin, hepatitis B virus, hepatitis B viral X gene
DOI: 10.3233/CBM-181498
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 135-144, 2018
Authors: Cai, Yu | Yan, Pu | Zhang, Ge | Yang, Wenqi | Wang, Haiping | Cheng, Xiaohu
Article Type: Research Article
Abstract: OBJECTIVE: Colorectal cancer (CRC) is the 3 rd most common cancer worldwide. Recently, long non-coding RNAs (lncRNAs) were found to be critical modulators in the CRC progression. The aim of this study is to investigate the potential roles of lncRNA P73 antisense RNA 1T (TP73-AS1) in CRC development and progression. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to determine relevant gene expression levels; western blot was performed to determine protein expression levels; CCK-8, colony formation, wound healing and Transwell invasion assays were used to determined CRC cell proliferation, migration and invasion; in …vivo tumor growth was assessed in xenograft mice model. RESULTS: TP73-AS1 was up-regulated in both CRC tissues and CRC cell lines. Overexpression of TP73-AS1 was associated with metastasis and advanced clinical stages in CRC patients. Overexpression of TP73-AS1 promoted CRC cell growth, proliferation, migration and invasion in vitro ; and knockdown of TP73-AS1 significantly inhibited CRC cell growth, proliferation, migration and invasion in vitro as well as tumor growth in vivo . Bioinformatics analysis and luciferase reporter assay indicated that TP73-AS1 could bind directly with miR-194, and TP73-AS1 negatively regulated the expression of miR-194 in CRC cells. Further study indicated that miR-194 negatively regulated the downstream target of transforming growth factor alpha (TGFα ) via targeting its 3’ untranslated region, and TP73-AS1 positively regulated the expression of TGFα in CRC cells. Moreover, overexpression of miR-194 suppressed CRC cell proliferation and invasion, and attenuated the effects of TP73-AS1 overexpression on CRC cell proliferation and invasion. Silence of TGFα inhibited CRC cell proliferation and invasion, and also reversed the effects of TP73-AS1 overexpression on CRC cell proliferation and invasion. CONCLUSIONS: this study demonstrated that TP73-AS1 regulated CRC progression by acting as a competitive endogenous RNA to sponge miR-194 to modulate the expression of TGFα . Show more
Keywords: Colorectal cancer, progression, TP73-AS1, miR-194, TGFα
DOI: 10.3233/CBM-181503
Citation: Cancer Biomarkers, vol. 23, no. 1, pp. 145-156, 2018
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