scholarly journals Differential Expression of Ribosomal Proteins in Human Normal and Neoplastic Colorectum

2003 ◽  
Vol 51 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Hide Kasai ◽  
Daita Nadano ◽  
Eiko Hidaka ◽  
Kayoko Higuchi ◽  
Masatomo Kawakubo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Proteins ◽  
Protein Biosynthesis ◽  
Secretory Granules ◽  
Expression Patterns ◽  
Normal Mucosa ◽  
Cellular Processes ◽  
Colorectal Mucosa ◽  
Colorectal Cancer Cells ◽  
Mucosal Cells

Ribosomal proteins are a major component of ribosomes and play critical roles in protein biosynthesis. Recently it has been shown that the ribosomal proteins also function during various cellular processes that are independent of protein biosynthesis therefore called extraribosomal functions. In this study we have, for the first time, determined the expression profile of 12 ribosomal proteins (Sa, S8, S11, S12, S18, S24, L7, L13a, L18, L28, L32, and L35a) in normal epithelia of human colorectal mucosa using immunohistochemistry (IHC) and then compared their expression patterns with those of colorectal cancer. In the normal mucosa, ribosomal proteins were largely associated with the ribosomes of mucosal epithelia, and the expression level of ribosomal proteins, except for S11 and L7 proteins, was markedly increased in associated with maturation of the mucosal cells. On the other hand, these ribosomal proteins were markedly decreased in colorectal cancer compared with the normal mucosa. By contrast, S11 and L7 ribosomal proteins were rarely associated with the ribosomes of colorectal epithlia except immature mucosal cells, whereas their expression levels were significantly enchanced in colorectal cancer cells. In addition, L7 ribosomal protien was detected in the secretory granules of the enterochromaffin cells in the colorectal mucosa and in carcinoma cells expressing chromogranin A. These results indicate that the expression of ribosomal proteins is differentially regulated not only in normal mucosa but also in carcinoma of human colorectum, and suggest an extraribosomal function of L7 ribosomal protein in neuroendocrine function.

scholarly journals High expression of Wnt7a protein predicts a poor survival in patients with colorectal carcinoma

2020 ◽  
Author(s):  
Congcong Li ◽  
Peilin Cui ◽  
Xiaowei Dou ◽  
Hongli Li ◽  
Jiahuan Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Malignant Tumors ◽  
Integration Site ◽  
Normal Mucosa ◽  
Lymph Node Involvement ◽  
Colorectal Adenomas ◽  
Future Research ◽  
Colorectal Mucosa ◽  
Staining Score

Abstract Background: Colorectal cancer is one of the most common malignant tumors in China, and the number of new cases and the number of cases of deaths has increased annually. However, its pathogenesis is still unclear. Wnt7a is a member of the wingless-type MMTV integration site family, and it plays an important role in tumorigenesis and development by controlling cell proliferation and differentiation as a secreted glycoprotein. Whether Wnt7a has the properties of an oncogene or not is an important focus for future research as this target has diverse roles in different tumors.Methods: Wnt7a protein expression in normal colorectal mucosa and colorectal tumors was detected via immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were used to explore the associations between Wnt7a staining score and various clinical parameters.Results: Wnt7a was strongly expressed in colorectal cancer tissues but weakly expressed in adjacent normal mucosa and colorectal adenomas. The level of Wnt7a expression was correlated with lymph node involvement (P < 0.001), Duke stage (P < 0.001), and cell differentiation (P < 0.001). Knockdown of Wnt7a inhibits proliferation of colon cancer cells and inhibits the ability of both colon cancer cell lines to migrate.Conclusions: Collectively, our results present evidence that Wnt7a is associated with an unfavorable prognosis of colorectal cancer.

scholarly journals Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression

2019 ◽  
Vol 20 (23) ◽  
pp. 5965 ◽  
Author(s):  
Elena Uleri ◽  
Claudia Piu ◽  
Maurizio Caocci ◽  
Gabriele Ibba ◽  
Francesca Sanges ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Simultaneous Detection ◽  
Normal Mucosa ◽  
T Antigen ◽  
Jc Polyomavirus ◽  
Paired Samples ◽  
Colorectal Mucosa ◽  
Viral Protein 1 ◽  
Coding Control

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient’s cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.

scholarly journals The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells

2018 ◽  
Vol 51 (6) ◽  
pp. 2547-2563 ◽  
Author(s):  
Jing Wang ◽  
Guangnan Liu ◽  
Mengwei Liu ◽  
Li Xiang ◽  
Yizhi Xiao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Expression Patterns ◽  
Gene Promoter ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Invasion Assays ◽  
Transcriptional Target

Background/Aims: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. Methods: The functional role of CCDC43 and FOXK1 in epithelial-mesenchymal transition (EMT) was determined using immunohistochemistry, flow cytometry, western blot, EdU incorporation, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. Results: The CCDC43 gene was overexpressed in human CRC. High expression of CCDC43 protein was associated with tumor progression and poor prognosis in patients with CRC. Moreover, the induction of EMT by CCDC43 occurred through TGF-β signaling. Furthermore, a positive correlation between the expression patterns of CCDC43 and FOXK1 was observed in CRC cells. Promoter assays demonstrated that FOXK1 directly bound and activated the human CCDC43 gene promoter. In addition, CCDC43 was necessary for FOXK1- mediated EMT and metastasis in vitro and vivo. Taken together, this work identified that CCDC43 promoted EMT and was a direct transcriptional target of FOXK1 in CRC cells. Conclusion: FOXK1-CCDC43 axis might be helpful to develop the drugs for the treatment of CRC.

scholarly journals Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Expression Patterns ◽  
Mrna Level ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Expression Level ◽  
Angiogenic Factor ◽  
Migration And Invasion ◽  
Aberrant Expression

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.

scholarly journals Wnt7a Promotes the Occurrence and Development of Colorectal Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Congcong Li ◽  
Xiaowei Dou ◽  
Jiahuan Sun ◽  
Min Xie ◽  
Hongli Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Colorectal Adenocarcinoma ◽  
Immunohistochemical Method ◽  
Regeneration Ability ◽  
Colorectal Mucosa ◽  
Colorectal Cancer Cells ◽  
Cloning Assay ◽  
Proliferation Ability

ObjectiveThe expression of Wnt7a in colorectal cancer tissues and cell lines was analyzed, and the effect of Wnt7a on the proliferation of colorectal cancer cells was studied, so as to confirm the relationship between Wnt7a and the occurrence and development of colorectal cancer.Methods(1) Immunohistochemical method was used to compare the expression of Wnt7a in different tissues and its relationship with the clinicopathology of colorectal adenocarcinoma. (2) The expression levels of Wnt7a in colorectal cancer cell lines HT-29 and HCT 116 were detected by qRT-PCR. (3) The down-regulated Wnt7A expression vector was constructed, and the down-regulated Wnt7A expression cell line was established. The regeneration ability of cancer cells was detected by stem cell ball formation assay, and the influence of plate cloning assay on the proliferation ability of colorectal cancer cells was detected.Results(1) The positive rates of Wnt7a in normal colorectal mucosa, colorectal adenoma and colorectal adenocarcinoma tissues gradually increased,Wnt7a are closely related to the degree of colorectal adenocarcinoma differentiation, lymph node metastasis and Duke stage. (2) The expression level of Wnt7a in colorectal cancer cells was higher than that in normal colorectal epithelial cells. (3) The down-regulation of Wnt7A reduced the proliferation ability of colorectal cancer cells.ConclusionsWnt7a promotes the occurrence and development of colorectal adenocarcinoma.

scholarly journals Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Expression Patterns ◽  
Mrna Level ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Expression Level ◽  
Angiogenic Factor ◽  
Migration And Invasion ◽  
Aberrant Expression

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.

Different small leucine-rich proteoglycans expression pattern by tumor location in colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15138-e15138
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Ivan Fernandez-Vega ◽  
Olivia García-Suárez ◽  
Natalia Perez Lopez ◽  
Luis M Quirós ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Core Protein ◽  
Expression Patterns ◽  
Normal Mucosa ◽  
Tumor Location ◽  
Healthy Tissue ◽  
Test Results ◽  
Molecular Phenotypes ◽  
Immunohistochemical Techniques ◽  
Specific Species

e15138 Background: Colorectal cancer (CRC) is a heterogeneous disease defined by anatomic, functional and molecular differences depending on the primary tumor location (PTL). Several molecular phenotypes have been associated with aggressive behavior, and some of these markers are related with proteoglycans, which in turn show alterations in CRC. Small leucine-rich proteoglycans (SLRPs) are a family of molecules encoded by18 genes that may appear coupled to different glycosaminoglycan chains ––including chondroitin/dermatan or keratan sulphate–– or not, depending on the specific species. They are ubiquitously expressed in extracellular matrices, and it’s been described their role in organ size and shape regulation during embryonic development. This study aims to investigate the expression patterns of SLRPs in CRC depending on the PTL. Methods: A transcriptomic approach was carried out by using qPCR to analyze SLRP core protein transcriptions in 32 tumor specimens and their respective healthy tissue: 12 right-sided & 20 left-sided. When significant differences were detected, immunohistochemical techniques were used to enhance the test. Results: While right-sided (R) CRC displayed significant alterations in 2 genes (biglycan BGN overexpression p = 0.015, osteoglycin OGN underexpression p = 0.048), left-sided (L) showed differences in 5 genes (BGN overexpression p = 0.0019 and underexpression of OGN p = 0.0016, prolargin PRELP p = 0.0049, chondroadherin CHAD p = 0.0180 and podocan PODN p = 0.0061). In L tumors CHAD was the most affected gen underexpressed by 16 times, while in R it was present in only 50% of healthy tissue. Transcripts for opticin and nyctalopin were not detected in most patients regardless of PTL. Lumican, decorin, keratocan, asporin, ECM2, fibromodulin, tsukushi, osteoadherin, osteomodulin, epiphycan and PODN-like 1 were detected with no significant differences compared to healthy tissue. Conclusions: Normal mucosa of the large bowel expresses most SLRP. BGN and OGN seem to be dysregulated in both L and R CRC, but CHAD, PRELP and PODN appear to show differences only in L CRC. These alterations could be related to the interaction with different ligands and modulation of homeostasis.

Alterations in small leucine-rich proteoglycans in right-sided colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 652-652
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Olivia Pilar García-Suárez ◽  
Ivan Fernández-Vega ◽  
Luis M Quirós ◽  
Beatriz García
Keyword(s):  
Colorectal Cancer ◽  
Dermatan Sulfate ◽  
Core Protein ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Normal Mucosa ◽  
Core Proteins ◽  
Molecular Phenotypes ◽  
Immunohistochemical Techniques ◽  
Specific Species

652 Background: Colorectal cancer (CRC) is a heterogeneous disease, and there are anatomic, functional and molecular differences between the tumors of the proximal and distal colorectum. Various molecular phenotypes have been associated with aggressive subtypes in these pathologies, and several of these markers show a relationship with proteoglycans, which in turn show significant alterations in colon tumors, which affect both their core proteins and their glycosaminoglycan chains. Small leucine-rich proteoglycans (SLRPs) constitute a family of molecules encoded by 18 distinct genes. They are grouped into five classes and may appear coupled to different glycosaminoglycan chains ––including chondroitin/dermatan sulfate or keratan sulphate–– or not, depending on the specific species. They are ubiquitously expressed in extracellular matrices, and have been found involved in the regulation of organ size and shape during embryonic development. In this study we investigate the expression patterns of SLRPs in right-sided CRCs. Methods: A transcriptomic approach was used, employing qPCR to analyze SLRP core protein transcriptions. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences of potential interest. Results: Only two proteins displayed significant alterations: biglycan appeared overexpressed approximately 4 fold (p = 0.015), and osteoglycin decreased about 4 fold (p = 0.05). Transcripts for epiphycan, opticin, nyctalopin and podocan-like 1 were not detected in most patients, while chondroadherin was detected in 50% of healthy tissues but not in CRCs. Expression of lumican, decorin, keratocan, asporin, ECM2, fibromodulin, PRELP, tsukushi, podocan and osteoadherin was detected, but with no significant differences compared to healthy tissue. Conclusions: Normal mucosa of the large bowel expresses most SLRPs, and two, biglycan and osteoglycin, appeared altered in right-sided CRCs. These alterations could be related to binding of different ligands and modulation of homeostasis.

scholarly journals Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3832
Author(s):  
Elena Lastraioli ◽  
Scott P. Fraser ◽  
R. Mine Guzel ◽  
Jessica Iorio ◽  
Lapo Bencini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Free Survival ◽  
Human Carcinomas ◽  
Clinical Biomarker ◽  
High Level

Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

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