CCX-CKR Expression in Colorectal Cancer and Patient Survival

2014 ◽  
Vol 29 (1) ◽  
pp. e40-e48 ◽  
Author(s):  
Yunxiang Zhu ◽  
Wentao Tang ◽  
Yun Liu ◽  
Guanghui Wang ◽  
Zhonglin Liang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Patient Survival ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Potential Value ◽  
Chemotactic Factors ◽  
Colorectal Cancer Patients ◽  
Negative Predictor

Colorectal cancer is one of the most common malignant cancers, with bad prognosis when distal metastasis occurs. The current study aimed to investigate the potential value of using CCX-CKR expression for the prognosis of colorectal cancer patients. The results showed that CCX-CKR expression was a negative predictor of cancer metastasis, and that it was positively correlated to the patients’ survival rate. Finally, we found that CCX-CKR expression in vitro could modulate cellular migration and invasion abilities, potentially via the regulation of other chemotactic factors/receptors.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

scholarly journals Expression of Long Non-Coding RNA PANDAR and its Prognostic Value in Colorectal Cancer Patients

2017 ◽  
Vol 32 (2) ◽  
pp. 218-223 ◽  
Author(s):  
Xiangke Li ◽  
Feng Wang ◽  
Yan Sun ◽  
Qingxia Fan ◽  
Guangfei Cui
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Human Cancer ◽  
Expression Level ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Relative Expression Level ◽  
Kaplan Meier ◽  
Colorectal Cancer Patients

Background Long noncoding RNAs (lncRNAs) are emerging as key molecules in human cancer. In the present study, we explored the role of the lncRNA PANDAR in colorectal cancer (CRC). Methods The relative expression level of lncRNA PANDAR in CRC tissues and cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between PANDAR expression and clinicopathological features of CRC patients were further analyzed. Kaplan-Meier survival analysis was performed to evaluate the value of PANDAR in the prognosis of CRC patients. Furthermore, the biological function of PANDAR on CRC cell growth, apoptosis and mobility was investigated through MTT, flow cytometry, transwell migration and invasion assays in vitro. Results The expression level of PANDAR was higher in CRC tissues and cells compared with adjacent nontumor tissues and normal colonic cell line NCM460. PANDAR expression was significantly correlated with local invasion, lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that patients with high PANDAR expression had poorer overall survival than patients with low PANDAR expression. Multivariate Cox regression analysis indicated that PANDAR might be an independent prognostic factor for CRC patients. Furthermore, PANDAR knockdown significantly inhibited cell proliferation, cycle progression, migration and invasion of CRC in vitro. Conclusions Our results suggest that high expression of PANDAR was involved in CRC progression and could act as an independent biomarker for prognosis of CRC patients.

scholarly journals lncRNA LINC00460 Functions as a Competing Endogenous RNA and Regulates Expression of BGN by Sponging miR-149-5p in Colorectal Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382096423
Author(s):  
Tingyan Ruan ◽  
Shourong Lu ◽  
Junying Xu ◽  
Ju-Ying Zhou
Keyword(s):  
Colorectal Cancer ◽  
Tumor Metastasis ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Expression Levels ◽  
Cancer Tissues

Background and Aim: There are an increasing number of studies indicating the important roles served by long non-coding RNAs (lncRNAs) in the development of different types of cancer. LINC00460 is a novel identified lncRNA that was found to be upregulated in colorectal cancer. However, the biological roles of LINC00460 in colorectal cancer have yet to be fully elucidated. This study was aimed to investigate the functions and molecular mechanisms of LINC00460 on colorectal cancer metastasis. Methods: Expression of LINC00460 and biglycan (BGN) in colorectal cancer tissues and cell lines were quantified by real time PCR or western blotting assay. Cell migration and invasion assays were performed to determine the effect of LINC00460 on tumor metastasis in vitro. The binding interaction between microRNA-149-5p and LINC00460 was revealed by luciferase reporter assay. Results: In the present study, lncRNA LINC00460 was shown to be upregulated in colorectal cancer tissues, and overexpression of LINC00460 significantly promoted metastasis of colorectal cancer in vitro. Furthermore, miR-149-5p interacted with LINC00460, and they negatively regulated expression of each other. Transfection of miR-149-5p mimics partially counteracted the tumor metastasis-promoting effects induced by LINC00460 overexpression. Finally, overexpression of LINC00460 upregulated the expression levels of biglycan, a target gene of miR-149-5p, which has also been identified as an oncogenic driver in colorectal cancer. Conclusion: Taken together, the present study demonstrated that LINC00460 promoted metastasis of CRC by sponging miR-149-5p and thereby affecting biglycan expression levels.

scholarly journals Aldolase B Overexpression is Associated with Poor Prognosis and Promotes Tumor Progression by Epithelial-Mesenchymal Transition in Colorectal Adenocarcinoma

2017 ◽  
Vol 42 (1) ◽  
pp. 397-406 ◽  
Author(s):  
Qingguo Li ◽  
Yaqi Li ◽  
Junyan Xu ◽  
Sheng Wang ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Enzymatic Reaction ◽  
Disease Free Survival ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Aldolase B

Background: Glycolysis is considered to be the root of cancer development and progression, which involved a multi-step enzymatic reaction. Our study aimed at figuring out which glycolysis enzyme participates in the development of colorectal cancer and its possible mechanisms. Methods: We firstly screened out Aldolase B (ALDOB) by performing qRT-PCR arrays of glycolysis-related genes in five paired liver metastasis and primary colorectal tissues, and further detected ALDOB protein with immunohistochemistry in tissue microarray (TMA) consisting of 229 samples from stage I-III colorectal cancer patients. CRISPR-Cas9 method was adopted to create knock out colon cancer cell lines (LoVo and SW480) of ALDOB. The effect of ALDOB on cell proliferation and metastasis was examined in vitro using colony formation assay as well as transwell migration and invasion assay, respectively. Results: In TMA, there was 64.6% of samples demonstrated strong intensity of ALDOB. High ALDOB expression were associated with poor overall survival and disease-free survival in both univariate and multivariate regression analyses (P<0.05). In vitro functional studies of CCK-8 demonstrated that silencing ALDOB expression significantly (P<0.05) inhibited proliferation, migration and invasion of colon cancer cells. Mechanically, silencing ALDOB activated epithelial markers and repressed mesenchymal markers, indicating inactivation of ALDOB may lead to inhibition of epithelial-mesenchymal transition (EMT). Conclusion: Upregulation of ALDOB promotes colorectal cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in colorectal cancer.

Use of serum CXCL16 to predict liver metastasis and prognosis in colorectal cancer patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 424-424
Author(s):  
K. Matsushita ◽  
Y. Toiyama ◽  
K. Tanaka ◽  
H. Yasuda ◽  
S. Saigusa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Cancer Patients ◽  
Serum Levels ◽  
Migration And Invasion ◽  
Poor Survival ◽  
Normal Volunteers ◽  
Colorectal Cancer Patients

424 Background: Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In CRC, serum levels of CEA have become well-established prognostic indicators. However, it is not generally accepted as optimal in its prognostic power. The aim of this study was to identify novel and reliable serum prognostic markers. Methods: We performed cytokine array to identify novel prognostic serum marker, and CXCL16 was selected. To investigate the relationships between sCXCL16 and clinicopathological findings including survival, the serum levels of CXCL16 in 237 CRC patients and 20 normal volunteers were assessed by enzyme-linked immunosorbent assay. Furthermore, we investigated proliferation, invasion and wound healing assay to investigate the biological role of CXCL16 to colon cancer cell by recombinant CXCL16 exposing to HT-29. Results: The mean sCXCL16 concentration in patients was significantly higher than that in normal volunteers (p<0.0001). In addition, sCXCL16 levels increased significantly in accordance with the progression of UICC stage classification (p < 0.05). In clinicopathologic findings, sCXCL16 was significantly associated with the presence of lymph node (p=0.019) and the presence of liver metastases (p=0.011). Elevated sCXCL16 level demonstrated a significant association with poor survival, and was an independent risk factor for poor survival. Furthermore, sCXCL16 was an independent marker for predicting liver metastasis (logistic analysis; p=0.0015). In vitro, recombinant CXCL16 promoted epithelial mesencymal transition (EMT) phenotype characterized by impaired E-cadherin and induction of Vimentin. In addition, CXCL16 promoted cell growth, migration and invasion. Conclusions: Our data demonstrate that preoperative sCXCL16 level increased in colorectal cancer patients, and that sCXCL16 correlated with liver metastasis, and is an independent prognostic factor for overall survival. Elevated CXCL16 has been proposed as a useful predictive marker for liver metastasis and overall survival in CRC. In vitro, CXCL16/CXCR6 axis might play an importance role in mediating cell survival, migration and invasion by EMT in CRC cell. No significant financial relationships to disclose.

scholarly journals Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPAA2B1

2020 ◽  
Author(s):  
Yu-Hui Zhang ◽  
Wei-Bin Huang ◽  
Yu-Jie Yuan ◽  
Jin Li ◽  
Jing Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Non Coding Rna ◽  
Potential Biomarker ◽  
Long Non Coding Rna

Abstract Background Long non-coding RNA H19 was demonstrated to be significantly correlated with tumor metastasis. However, the specific functions of H19 in colorectal cancer (CRC) metastasis and the underlying mechanism are still largely unclear. Methods Use public database to screen the potential lncRNA crucial for metastasis in colorectal cancer. The expression of H19 in clinical CRC specimens was detected by qRT-PCR. The effect of H19 on the metastasis of CRC cells was investigated by transwell, wound healing assays, CCK-8 assays and animal studies. The potential proteins binding to H19 was identified by LC-MS and verified by RNA immunoprecipitation (RIP). The expression of indicated RNA and proteins were measured by qRT-PCR or western blot. Results We found the expression of lncRNA H19 was significantly upregulated in primary tumor and metastatic tissues, correlated with poor prognosis in CRC. Ectopic H19 expression promoted the metastasis of colorectal cancer cells in vitro and in vivo , and induced epithelial-to-mesenchymal transition (EMT). Mechanistically, H19 directly bound to hnRNPA2B1. Knockdown of hnRNPA2B1 attenuated the H19-induce migration and invasion in CRC cells. Furthermore, H19 stabilized and upregulated the expression of Raf-1 by facilitated the interaction between hnRNPA2B1 and Raf-1 mRNA, resulting in activation of Raf-ERK signaling. Conclusions Our findings demonstrate the role of H19/hnRNPA2B1/EMT axis in regulation CRC metastasis, suggested H19 could be a potential biomarker to predict prognosis as well as a therapeutic strategy for CRC.

scholarly journals Metformin Inhibits the Development and Metastasis of Colorectal Cancer

2021 ◽  
Author(s):  
Kiyoaki Sugiura ◽  
Koji Okabayashi ◽  
Ryo Seishima ◽  
Takashi Ishida ◽  
Kohei Shigeta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Liver Tumors ◽  
Immunohistochemical Analysis ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Anti Cancer

Abstract BackgroundMetformin is a commonly used drug for the treatment of diabetes. Accumulating evidence suggests that it exerts anti-cancer effects in many cancers, including colorectal cancer. However, the underlying molecular mechanisms of colorectal cancer metastasis remain unclear.MethodsColorectal cancer cell lines were treated with metformin, and cell proliferation, invasion, and migration were analyzed in vitro. The relationship between metformin and the AMPK–mTOR axis was assessed by western blot analysis and transfection with small interfering RNA. A colorectal cancer xenograft mouse model was used to observe the effects of metformin on liver metastasis. Immunohistochemical analysis was performed on liver metastatic tumors.ResultsIn in vitro experiments, metformin significantly inhibited the proliferation, migration, and invasion only in HCT116 and SW837 cells, but not in HCT8 and Lovo cells. Only in HCT116 and SW837, a change in AMPK–mTOR expression was observed in a dose-dependent manner. In colorectal cancer xenograft mice, the liver metastatic rate (10% vs. 50%, p = 0.05) and the number of liver metastatic nodules (0.1/body vs. 1.2/body, p = 0.04) were significantly lower in the metformin group. Tumor proliferation and EMT were decreased and apoptosis was promoted only in metastatic liver tumors of mice treated with metformin.ConclusionThe molecular mechanism of the anti-cancer effects of metformin involves repression of mTOR pathways via AMPK activation. Moreover, the differences in metformin sensitivity depend on the response of the AMPK–mTOR pathway to metformin. Our study provides a theoretical basis for the anti-metastatic treatment of colorectal cancer using metformin.

scholarly journals Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients

2021 ◽  
Author(s):  
Ori Hassin ◽  
Nishanth Belugali Nataraj ◽  
Michal Shreberk-Shaked ◽  
Yael Aylon ◽  
Rona Yaeger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Regulatory Elements ◽  
Migration And Invasion ◽  
Missense Mutations ◽  
Oncogenic Signaling ◽  
Transcriptional Signature ◽  
Colorectal Cancer Patients

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide. The TP53 gene is mutated in approximately 60% of all CRC cases. Sporadic CRC is characterized by high prevalence of TP53 hotspot missense mutations. In particular, over 20 percent of all TP53-mutated CRC tumors carry either the p53R175H structural mutant or the p53R273H DNA contact mutant. Importantly, clinical data analysis suggests that CRC tumors harboring p53 R273 mutations are more prone to progress to metastatic disease than those with R175 mutations, in association with decreased survival. By combining in vitro CRC cell line models and human CRC data mining, we identified a unique transcriptional signature orchestrated by p53R273H, implicating activation of oncogenic signaling pathways and predicting worse patient outcome. Concordantly, p53R273H selectively promotes rapid CRC cell spreading, migration and invasion in vitro and metastasis in vivo. Mechanistically, the transcriptional output of p53R273H is associated with, and presumably driven by, its preferential binding to regulatory elements of R273 signature genes. Together, this demonstrates that different TP53 missense mutations contribute differently to cancer progression, and that p53R273H possesses distinct gain-of-function activities in CRC that bear on disease course and possibly on patient management strategy. Given that practically all current analytical cancer gene panels include TP53, elucidation of the differential impact of distinct TP53 mutations on disease features is expected to make information on TP53 mutations more actionable and holds potential for better precision-based medicine.

scholarly journals SRGN Promotes Colorectal Cancer Metastasis as a Critical Downstream Target of HIF-1α

2018 ◽  
Vol 48 (6) ◽  
pp. 2429-2440 ◽  
Author(s):  
Yang Xu ◽  
Jie  Xu ◽  
Yanfang Yang ◽  
Lei Zhu ◽  
Xubin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Potential Candidate ◽  
Metastatic Progression ◽  
Downstream Target ◽  
Underlying Mechanisms

Background/Aims: The chondroitin sulfate proteoglycan serglycin (SRGN), a hematopoietic cell granule proteoglycan, has been implicated in promoting tumor metastasis; however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate the SRGN gene expression and its regulation as downstream signaling of hypoxia-inducible transcription factor 1 alpha (HIF-1α) in colorectal cancer (CRC) cells and tissues. Methods: The expression of SRGN was analyzed in CRC specimens for its correlation with progression and metastasis. Using chromatin-immunoprecipitation (ChIP), quantitative real-time PCR, Western blot, and transwell assay, the functional role and underlying mechanism of SRGN in CRC metastasis were elucidated. Thus, this study provides evidence of a critical role of SRGN in metastatic progression of CRC. Results: Our results indicated that SRGN overexpression was significantly associated with poor prognosis in CRC specimens. SRGN overexpression promoted CRC cell migration and invasion in vitro; however, SRGN depletion exhibited contrasting effects. Mechanistic investigations revealed that HIF-1α regulated SRGN transcription via physically binding to a hypoxia response element in its promoter region. Conclusions: In conclusion, we demonstrated that dysregulated HIF-1α/SRGN signaling promotes CRC progression and metastasis. SRGN may serve as a potential candidate therapeutic target for metastatic CRC.

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